Systems, methods and kits for peripheral nerve stimulation

ABSTRACT

Nerve stimulation systems and methods are disclosed for providing modulation of nerve targets in the lower limbs typically at or below the knee. For example, transcutaneous electrical nerve stimulation (TENS), percutaneous nerve stimulation, and implantable stimulation systems and methods are disclosed for providing stimulation to the saphenous nerve (SAFN). Additionally, systems and methods are provided for co-stimulating the posterior tibial nerve (PTN) and SAFN in combination with unique stimulation, and with control and display of OAB therapy protocols for multiple sites. Systems and methods of treatment can provide for management of usage and compliance monitoring, obtain and operating upon patient input responses to queries and management of payments and permissions related to provision of therapies for various disorders. Monitoring of usage and compliance can be managed both locally and remotely from a user. Stimulation provided in combination with a passive implantable component is also disclosed.

REFERENCE TO RELATED APPLICATIONS

This Patent Application claims the benefit of U.S. Provisional Patent Application Ser. No. 62/375,898 filed 16 Aug. 2016 and is a continuation-in-part of patent application Ser. No. 15/439,415, filed 22 Feb. 2017, currently pending, which is a continuation of Ser. No. 15/160,468, now U.S. Pat. No. 9,610,422, which claims the benefit of U.S. Provisional Patent Application Ser. No. 62/171,549 filed 5 Jun. 2015, and Ser. No. 62/165,037 filed 21 May 2015; and is a continuation-in-part of patent application Ser. No. 15/160,585, filed May 20, 2016 entitled Systems and Methods for Improved Treatment of Overactive Bladder which is a continuation-in-part of patent application Ser. No. 14/553,427, filed Nov. 25, 2014 entitled Systems and Methods of Enhancing Electrical Activation of Nervous Tissue which is based upon of Provisional Patent Application Ser. No. 61/909,679, filed 27 Nov. 2013; Provisional Patent Application Ser. No. 61/944,744, filed 26 Feb. 2014; and, Provisional Patent Application Ser. No. 62/024,912, filed 15 Jul. 2014.

INCORPORATION BY REFERENCE

This Patent application hereby incorporates by reference, U.S. patent application Ser. Nos. 15/160,468 and 14/553,427, and U.S. Patent Applications Ser. Nos. 61/909,679, 61/944,744, 62/024,912, 62/165,037, 62/171,549, and 62/375,898, which are hereby incorporated by reference in entirety for all purposes.

FIELD

The subject concept relates to the field of modulating biological tissue.

BACKGROUND

Nerve stimulation (neurostimulation) technology includes applications such as electrical neuromodulation, functional electrical stimulation, and therapeutic electrical stimulation. Nerve stimulation is an effective clinical tool used to treat various chronic medical disorders and conditions. Examples include (1) deep brain stimulation (DBS) for treating Parkinson's disease and essential tremor, (2) spinal cord stimulation for treating pain and voiding disorders, and (3) peripheral nerve stimulation for treating pelvic floor disorders and dysfunctions (e.g., overactive bladder), pain, obstructive sleep apnea, headache, migraine, epilepsy, depression, hypertension, cardiac disorders, and other disorders and disease states. Peripheral nerves may include, for example, the vagus nerve, occipital nerve, cranial nerves, spinal nerves, pudendal nerves, cutaneous nerves, and the sciatic and femoral nerves.

The peripheral nervous system provides a neural substrate that allows nerve stimulation to treat various disorders. Long-term viability of implanted neurostimulators can be complicated by issues related to repeated mechanical movement (e.g., lead fracture and/or component migration). Transcutaneous electrical nerve stimulation (TENS) can provide a more simple and non-invasive approach. However, selective nerve activation by TENS may not be readily achieved due to, for example, intervening tissue or distance between a nerve target and the skin surface. Accordingly, some therapies rely on percutaneous stimulation in order to stimulate a target nerve.

Advances in minimally-invasive nerve stimulation have been realized clinically. Wireless implantable electrode probes have been developed for achieving less invasive methods of selective nerve stimulation. The BION (Advanced Bionics) is a glass or ceramic covered electrode that can be percutaneously injected into a region of interest. It can be self-powered or passively charged by radio frequency (RF) pulses. Long-term use may be complicated by migration of the BION from its original implant location. This migration may cause both reduced therapeutic effects and increased stimulation-evoked side effects due to activation of other (non-target) tissue. Nerve stimulation systems (e.g., MicroTransponder Inc. SAINT™ System) which are smaller, less expensive, and/or less technically complicated than the BION may be advantageous in treatment of some disorders. StimGuard has developed injectable implantable neurostimulators, which use wireless power in the RF and/or microwave frequency rage and non-inductive antennas which receive electromagnetic energy radiated from a source located outside of the patient's body. Energous technology is developing wireless technology that utilizes multiple antennae to provide improved transmission and harvesting of wireless energy and is developing within the implantable device space. These innovative technologies will allow smaller form factors. Witricity is using wireless magnetic induction technology to power implanted devices. Alternatively, Valencia Technologies has developed a coin-shaped implantable neurostimulator disclosed, for example in US App Nos. 20140214128A1, US20140214144A1, US20150148864A1, (all to Peterson et al.), which has a battery which may not be rechargeable, and which can last 2-3 years when providing periodic stimulation for disorders such as overactive bladder.

Transcutaneous magnetic stimulators (TMS), termed “transcranial magnetic stimulators” when used for brain stimulation, are used to treat disorders such as migraine (e.g. those made by Neuralieve Inc. such as U.S. Pat. Nos. 7,294,101, 8,262,556) by using an external magnetic stimulation device to stimulate central or peripheral tissue targets. The fields induced inside the tissue by one or more pulses (e.g., such as may occur with pulsed electromagnetic stimulation) may be less localized than desired. The present invention may offer advantages related to enhancing the effects of externally applied magnetic and/or electrical fields near a target nerve.

In addition to pain treatment, TENS systems have been used to apply electrical fields to the brain in order to modulate sleep, anxiety, depression, pain, attention, memory, and various types of brain activity. Tens systems are being developed to enhance performance of athletes by stimulating a person's head, although the mechanisms of action are not fully understood. TENS is not currently used to reliably treat certain disorders such as overactive bladder. This may be due, at least partially, to the difficulty of modulating the posterior tibial nerve which is typically too deep for the TENS signal to reliably reach. The disclosed systems and methods may allow a TENS system to stimulate novel anatomical areas and nerve targets in the treatment of overactive bladder.

The first largely available percutaneous nerve stimulation method and system for treatment of overactive bladder was provided by Uroplasty under the name “Urgent PC”. The therapy involves posterior tibial nerve stimulation using a percutaneous needle electrode at a site above and posterior to the patient's medial malleolus which stimulates in conjunction with an electrode attached to the medial side of a patient's foot. The method and system has been described in U.S. Pat. Nos. 6,493,588, 7,668,598, 8,046,082, 8,812,114, 9,056,194, 9,265,941 assigned to Uroplasty. The Urgent PC system design incorporates a “use” status when the device is ready to provide therapy and a “do not use” status when the device is not ready. The device works with a lead set having a status flag element with a “use” status which converts to a “do not use” status at a predetermined time after start the therapy. The status change includes blowing a fuse of the lead set so that the lead cannot be re-used for subsequent therapy. Single-use leads require a new lead must be purchased and used for each subsequent provision of therapy.

A more recent alternative percutaneous nerve stimulation method and system has been described in U.S. Pat. No. 8,660,646 entitled “Percutaneous tibial nerve stimulator” to Laing et al. The disclosure describes a system developed by Advanced Uro-Solutions and now distributed under the name NURO by Medtronic. The system uses a method that includes providing a computer system having a customer interface and a neurostimulator unit that is operated in conjunction with the interface. The neurostimulator has a pulse generator that is electrically coupled to a transcutaneous electrode configured to be applied to skin of a patient (e.g. inner foot) and a percutaneous electrode for insertion at stimulation site of a patient which is the posterior tibial nerve. A microcontroller communicates with the pulse generator and allows for the monitoring of how many treatment credits are available to be used by the neurostimulator. If there is at least one treatment credit, the microcontroller allows for activating the pulse generator and decrements the treatment credit counter when a treatment is provided to a patient. The system also provides for a computer system that can receive a treatment credit request transmitted through the customer interface and adjusting the number of treatment credits available based on the number of treatment credits purchased. Accordingly, the system allows for treatment to be accomplished as long as the treatment has been paid for by obtaining a treatment-credit beforehand.

These prior art systems suffer a number of limitations. These provide a single stimulator (e.g., configured to provide a single percutaneous electrode for insertion at a single treatment site near the ankle). More than one stimulation site may be beneficial and stimulating the saphenous nerve near the knee may have advantages. Stimulation systems may not allow for providing more than one treatment across a period of time (e.g., 3- or 24-hours) although all treatments may be related to a single event or disorder, but with greater severity, requiring a larger “dose”. For example, treatment credits are related to a single stimulation session lasting a particular duration.

The prior art percutaneous stimulation devices for treatment of OAB by stimulation of the poster tibial nerve (PTN) suffer a number of additional disadvantages and limitations. For example, they are designed for percutaneous stimulation of the PTN rather than for PTN or TENS of the saphenous nerve, or for a combination (e.g. first percutaneous and then TENS). The SAFN which may be more sensitive to, and offer an additional mechanism for, stimulation intended to modulate bladder activity.

Another disadvantage is that prior art stimulators are not configured to adjust stimulation parameters for, and then provide stimulation with, signals provided at two or more percutaneous stimulators that are applied to the patient to provide stimulation of targets including, for example, both the PTN and the SAFN. There is no provision for display of different stimulation parameters related to two or more targets.

Another disadvantage is that prior art stimulators (e.g. percutaneous, magnetic, etc) used for treatment various conditions implement a pay-per-session paradigm. For example, in the treatment of OAB (or migraine) there is a charge to stimulate at a single stimulation site. This does not allow for stimulating using 1 or more neurostimulators or needles at two stimulation sites. This also does not allow for requiring payment to activate a device for a single interval of use rather than for a plurality of uses within that interval (e.g. several therapy sessions on a particular day).

Another disadvantage is that prior art TENS stimulators (which work either jointly, with or without, implanted components) are not configured to provide treatment related to overactive bladder with features that promote compliance and therapy benefit. Prior art TENS stimulators are also not configured to provide stimulation of the saphenous nerve in the treatment of overactive bladder or other pelvic floor disorder.

Systems and methods are needed which provide advantages for both clinic-based and home-based therapy such as one or more of the following: a) providing at home stimulation treatment to patients contingent upon a subscription being valid; b) allowing for providing a selected number of treatments within the course of a selected, and programmable, treatment window such as a 6, 12, 24 or 48 hour period, or an interval of weeks or months; c) monitoring, recording, displaying, reporting, sending and operating upon usage data related to treatment times, durations, compliance, non-compliance, and other characteristics of patient use; d) alerting doctors, caregivers, or patients to promote compliance and/or when non-compliance or incorrect-use occurs; e) providing the selection of session-based, dose-based, interval-based, local-based and remote-based use-management; and, f) providing TENS systems configured for OAB treatment and/or stimulation of the saphenous nerve to provide treatment of other disorders or provide other benefit.

SUMMARY

In an embodiment, a transcutaneous tissue stimulation system and method is provided which includes one or more electrical generators positioned external to a patient. Stimulators which are either needle or TENS electrodes are electrically coupled to the one or more electrical generators and are positioned on the surface of, or penetrate, the patient's skin. Multiple target nerves may be defined with different stimulation protocols as part of the treatment program.

In embodiments, systems and methods are provided for achieving effective therapeutic nerve activation of the SAFN with TENS of the medial portion of a patient's leg between approximately the knee and the medial malleolus which can enable a primarily home-based TENS therapy treatment for OAB to become a simple and attractive (e.g. first-line) treatment option similar to lifestyle changes, or a second line treatment option to be used rather than drug therapy, since this does not require ongoing, frequent clinic-visits for percutaneous intervention.

In embodiments, stimulation systems and methods are described for providing advantages related to increasing therapeutic efficacy of nerve stimulation, improving the comfort of a patient relative to alternative therapeutic solutions, increasing patient compliance, decreasing the cost of treatment, and/or providing for a simple treatment using external and/or implanted components.

In embodiments, an implanted, electrically conductive member is positioned on, or contiguous to, a target nerve tissue for stimulation of the target nerve tissue to modify the electrical field signals generated by the electrical generator and provided by the stimulator for the purpose of modulating signals from the nerve tissue to the brain, to the central or peripheral nervous system, or other target, of the patient. System and methods aim to avoid activation of non-targeted nervous tissue, which can both limit the overall therapeutic effects and exacerbate stimulation-evoked side effects. The implanted passive element is configured to allow therapy to achieve the same, or improved therapeutic benefit as that which would otherwise be achieved when using only transcutaneous nerve stimulation without an implanted passive element. The systems and methods for providing stimulation of tissue using complementary or “paired” configurations of external stimulation elements and subcutaneously implanted passive elements.

Another objective is to provide systems and methods for achieving effective therapeutic nerve activation with relatively lower stimulation amplitude and/or shorter pulse width than what is typically achievable using prior art methods (e.g., TENS).

While the systems and methods disclosed herein are generally oriented for peripheral stimulation, these may also be applied to stimulation of other targets of the spine, brain, or body.

These and other objectives and advantages of the invention will now be disclosed in the figures, detailed description, and claims of the invention.

In the illustrated embodiments, any steps shown in the figures may occur in a different order, may be repeated, may lead to different steps of the method shown within each figure, or may lead to steps shown in other figures. Steps and components shown may be included or excluded from a particular embodiment, and this may occur conditionally, or according to the system or treatment protocol implemented by a therapy program. The therapy program may be implemented partially or fully by one or more processors of a medical system which may include an external, or a partially or fully implantable neurostimulator. The therapy program can be adjusted according to control by, or therapy plan implemented by, a patient, doctor, remote medical service, or caregiver.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a view of a neurostimulation system applied to a patient for stimulating the saphenous and posterior tibial nerve targets according to an embodiment of the invention;

FIG. 2 is a view of a neurostimulation system having two neurostimulator devices applied to portions of separate legs of a patient according to an embodiment of the invention;

FIG. 3A is a view of a neurostimulation system having two neurostimulator devices applied to two portions of a single leg of a patient according to an embodiment of the invention;

FIG. 3B is a view of a TENS electrode linking system for linking the TENS circuits of two neurostimulator devices according to an embodiment of the disclosure;

FIG. 4 is a view of a neurostimulation system applied to a leg of a patient for providing percutaneous stimulation according to an embodiment of the disclosure;

FIG. 5 is a view of a neurostimulation system applied to a leg of a patient for providing transcutaneous stimulation according to an alternative embodiment of the disclosure;

FIG. 6A is a view of target locations for a neurostimulation system applied to a back of a patient for providing transcutaneous stimulation according to an alternative embodiment of the disclosure;

FIG. 6B Shaded anatomical plot of the sensation perceived during SAFN stimulation, showing that as the amplitude was increased from threshold skin (Tskin) to threshold where discomfort was experienced (Tlimit), the evoked sensation spread across the entire medial aspect of the lower leg, down to the ankle (N=15 subjects).

FIGS. 7A and 7B show two displays related to patient compliance that can be provided by a compliance module of a neurostimulator system.

FIG. 8 is a schematic diagram of a neurostimulator system and functional modules which may be used to realize embodiments of the current invention including the provision of tissue stimulation.

FIG. 9 is a schematic block diagram of circuitry that supports the functional modules of an embodiment of a neurostimulator system.

FIGS. 10A and 10B are views of example displays that serve as user interfaces in an embodiment of the system.

FIGS. 11A,B,C show alternative TENS accessories and embodiments for use with the current invention.

FIG. 12 shows a flow chart of a method for providing therapy.

FIGS. 13A and 13B show additional flow charts of a method for providing therapy.

FIG. 14 shows a TENS system having an electrode array and a neurostimulator.

FIG. 15 shows a top and bottom portion of a neurostimulator.

FIG. 16 plots the selectivity ratio (SR), which shows the relative activation of TN/SAFN by PTNS was strongly dependent on the depth and anterior-posterior position of the uninsulated (top row) and insulated (bottom row) needle.

FIG. 17 plots the percentage change in the selectivity ratio, which quantifies the relative activation of the TN in comparison to each individual SAFN branch (A to E), that resulted when the uninsulated needle was replaced with an insulated needle electrode.

FIG. 18 plots the percentage of SAFN branches that are activated by PTNS simulated at varying stimulation amplitudes. The results obtained with an uninsulated needle electrode (top row) are compared to those obtained with an insulated needle electrode

FIG. 19 plots the average electrode-to-nerve distance that achieves activation of one or more SAFN branches. Simulations were conducted at multiple stimulation amplitudes (0.5 T to 4 T).

FIG. 20 shows amplitude stimulation trials (10-minutes each) for different frequencies, with 20 Hz resulting in the most significant reduction of average bladder contraction rate (BCR).

FIG. 21 plots the effectiveness of SAFN stimulation as percentage of experiments showing decreased BCR both during (intra) and after (post) stimulation.

FIG. 22 shows a screen related to querying patients about the number of trips they made to the bathroom.

FIG. 23 shows a screen related to querying patients about the urgency related to voiding.

FIG. 24 plots the percentage of experiments in which loss of bladder function was observed in response to SAFN stimulation (25 μA) applied at different pulse frequencies (10 Hz and 20 Hz) and stimulus durations (10 min, 20 min, and 40 min).

FIG. 25 plots prolonged changes in bladder function following SAFN stimulation (25 μA, 10 Hz, 40 minute duration) in anesthetized rats.

FIG. 26 shows a cross section of the human lower leg model that was used to simulate PTN activation with surface TENS electrode.

FIG. 27 shows a lateral view of the lower leg model with an implanted passive component (IPC) in the form of a nerve cuff.

FIG. 28 shows a cross section schematic of a patient's skin, a TENS electrode, an IPC, and an underlying target nerve.

FIGS. 29A-C plot the change in neural excitability that is achieved with eTENS. This is expressed by the relative excitation, which was determined by comparing either the activating function (AF) or the nerve activation thresholds predicted by the MRG model. The effects of eTENS was determined at multiple locations along the length of the nerve.

FIG. 30 shows the effects of the electrical conductivity of the IPC on the relative excitation achieved by eTENS.

FIG. 31 shows the effects of the IPC length on the relative excitation achieved by eTENS.

FIG. 32 shows the change in the electrical potential along a single axon within the target nerve that is caused by the IPC. The conductive cuff (IPC) generates an isopotential region and also sharp potential gradients at both edges of the IPC.

FIG. 33A compares the simulated radial current measured during TENS and eTENS, using the same monopolar surface electrode.

FIG. 33B, compares the simulated longitudinal current flowing through the endoneurium during TENS and eTENS.

FIG. 33C, shows changes in the simulated ratio of radial currents both with and without the presence of an electrode cuff that works in conjunction with a monopolar TENS electrode.

FIG. 33D, shows changes in the simulated ratio of axial currents both with and without the presence of an electrode cuff that works in conjunction with a monopolar TENS electrode.

FIG. 34A, shows changes in the simulated current density with the presence of a nerve cuff that works in conjunction with a monopolar TENS electrode, and demonstrates that the change in orientation of current density is greatest at the proximal and distal tips of the passive nerve cuff (represented in the figure with dotted rectangular pattern).

FIG. 34B, shows how the activating function changes as a position along the length of the nerve of the figure above and indicates that the positive and negative AF at the edges of the cuff correspond to greatest degree of nerve depolarization and hyperpolarization.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Reference will now be made in detail to exemplary embodiments of the present disclosure, examples of which are illustrated in the accompanying drawings. Where possible, the same reference numbers will be used throughout the drawings to refer to the same or like components. When titles are provided for different sections of this disclosure these are merely to highlight certain themes and are not meant to limit the invention concept.

FIG. 1 shows an embodiment of neuro stimulation system 10 applied to a patient for stimulating one or more targets in the leg of a patient 6 which in this example are a saphenous nerve target and posterior tibial nerve target. The neurostimulator 50 has a housing 12 and a power button 14 for turning the device on and off. A set of dedicated button controllers 16 (labeled 1, 2, and 3 in the figure) provide functionality such as for starting stimulation (e.g. beginning a treatment session that will last a selected time interval), pausing stimulation, and halting stimulation. The “pause” function can allow the therapy to be paused and restarted within a specified interval after the stimulation is started without blowing a fuse of the electrode lead set (Uroplasty type system) or decrementing the treatment credit (Nuro type system). This can allow for the needle to be repositioned if needed. A menu controller 18 operating in conjunction with the user interface module 76 allows a user to navigate through a set of menu options presented on the display 20 to select and/or adjust operation of the system 10. For example, a user can adjust a therapy protocol parameter such as the amplitude of at least one stimulation signal that may be selectively provided to one, two, or more stimulators such as a first and second percutaneous needle electrode 28 a, 28 b. The display 20 is configured to present a user with information about stimulation parameter values related to stimulation of at least a first target (e.g. SAFN) and also a second target (e.g. TN) when two or more stimulation targets are modulated during therapy for overactive bladder or other disorder.

A conduit connector 22 is formed as a plug that connects the neurostimulator 50 to a lead set 24. In an embodiment, the lead set connects to a first lead 84 which connects to a surface stimulator TENS electrode 88 and a second lead 86 which is multi-stranded and branches into individual wires 86 a and 86 b, which may be single or multi-stranded, and which provide the stimulation signals to two needle electrode clips 26 a, 26 b. In an alternative embodiment, stimulation is only delivered to the SAFN and a single wire 86 b, clip 26 b, and needle electrode 28 b are provided. In other words, lead set 24 can communicate the stimulation signal to the TENS electrode 88 and only to one needle holder 26 b, when only 1 percutaneous needle stimulator is used. The system 10 may also be designed so that stimulation signals travel between the two needle electrodes 28 a, 28 b and a TENS electrode 88 is not provided.

In the illustrated embodiment, needle electrode 28 a is inserted percutaneously at a first location cephalad and posterior to the medial malleolus, while needle electrode 28 b is inserted at a second location to stimulate the SAFN, such as a location cephalad and anterior to the medial malleolus. The surface electrode 88, is positioned on the medial surface of a foot of a patient 6 (other locations below or above the ankle are also viable).

The display 20 shows a setting of “6”, reflecting amplitude or strength of the stimulation signal applied at needle electrode 28 b for “SF” (i.e. SAFN) stimulation, while “10” reflects amplitude of stimulation applied at the PTN site. The user has selected a stimulation protocol parameter value of “Same” which indicates that the stimulation is supplied to the SAFN and PTN at the same time, rather than “Alt” which would cause the sites of stimulation therapy to alternate. Alternating may include, for example, periodically stimulating for 5 minutes at the first target site followed by 5 minutes at the second, and so on. Alternating can also include stimulating at 10 Hz at both SAFN and PTN, with two stimulation signals that are time lagged to be out of phase such that the combined signal of the 2 interleaved series of pulses is 20 Hz.

The display 20 can also indicate additional information such as a timer value showing the duration of the therapy that has occurred (or the duration remaining), remaining battery charge, stimulator and/or sensor impedance values, errors or faults (e.g., the neurostimulator did not receive a scheduled maintenance or calibration). Information about wireless data and/or power communication strength (or connection status), related to communicating power or data signals between different component of the neurostimulation system 10 and/or the neurostimulator 50 may also be shown. In addition to the display 20, the neurostimulator 50, can also use LEDs 92 a/156 situated on the housing 12 in order to indicate a status of a measure such as impedance (e.g. green=good) or to alarm/alert the user about the status of therapy or device operation. The display 20 can be much larger than that shown in the figure, and may be supplied on a user programmer 70 to enable clear presentation of graphs and tables related to usage and compliance. In an embodiment, the display 20 can also display treatment credit information.

In alternate embodiments, either the graphic display 20 or some of the user interface controllers may be realized as detachable from the neurostimulator housing 12. For example, the neurostimulator 50 may be controlled by a user who has established wireless communication link between it and a smartphone, tablet, laptop or other device, that may serve as type of user programmer 70. Remote controlling of the device 50 can be provided in addition to, or as an alternative to, the user input buttons 18 and display 20 on the housing 12. The neurostimulator 50 can communicate using wireless signals (e.g., infrared, Bluetooth, WIFI) or by wired connection, and can send data over the internet. A user's laptop can be provided with a software application that provides instructions to a processor for linking with, and subsequently control of, at least one neurostimulator 50 as well as serving as a display/controller device. Either the neurostimulator or the linked device can operate to notify a user (patient or administrator) by sending a visual, sonic, or other alert signal indicating a status or parameter value related to the provision of treatment using the user interface module 76 and related alerting components 156.

Typically a stimulation signal with a fixed frequency (e.g., 20 Hz and a pulse width of 200 msec) is increased until a behavioral response is seen such as flexion of the big toe or fanning of all toes becomes visible, or until a subjective response is made (e.g., tingling sensation is reported radiating towards the foot or toes). However in some patients, such as those with diabetes and various neuropathies, a subjective report may not be accurate or subjects may be unsure of whether a nerve is being stimulated for various reasons. Using sensor data can enable the detection of a quantitative measure such as a motor evoked response. In an embodiment, a second connector 23 connects the neurostimulator 50 to a lead set 85 which connects to at least one sensor such as a disposable TENS surface electrode 88 b. In order to monitor nerve or muscle activity (e.g., EMG), the TENS electrode 88 b can be realized with two electrical contacts. Alternatively, two disposable TENS surface electrodes can be attached to the lead set 85. The neurostimulator 50 is configured to provide sensing and evaluation of a signal related to the provision of therapy, such as an EMG signal, using the sensing and processing modules 55, 58 in order to detect a person's foot twitch (toe flex or fan, or extension of entire foot). of toes in response to the stimulation of the PTN. Alternatively, measuring “muscle twitch” activity could occur using a strain gauge embedded with a sock or realized in an adhesive band-aid like form factor (which may look like a surface electrode and use a bonded metallic strain gauged design). Flexion or twisting of the strain gauge will cause change in voltages that signals efferent activation.

FIG. 2 shows an alternative embodiment of a neurostimulation system 8 for stimulating a first and a second nerve target in a first and second leg of a patient. In this case the first target is an anterior branch SAFN target on the first foot (left side of figure) and the second is a PTN target on the second foot (right side of figure). A first and second neurostimulator 51 b, 51 a are configured to provide stimulation to the SAFN via first needle stimulator 28 b and PTN using second needle stimulator 28 a (the end of the conduit 86 can be attached to a needle holder which, in turn, attaches to the needle 28, as in FIG. 1, but this is not shown to avoid cluttering of the figure). As shown, the top surface of the neurostimulator has displays and buttons and faces away from the page. A disposable TENS electrode 88 a, 88 b can be attached to the bottom surface of each neurostimulator 51 a, 51 b (e.g. the electrode can snap onto an electrically conductive snap on the bottom side of the stimulator) in order to complete the stimulation circuit for each foot. This configuration may be useful, for example, in patients who are receiving stimulation therapy for both the SAFN and PTN, but who have trouble tolerating (or have difficulty in being able to distinguish or assess) stimulation of both targets in the same leg. In an alternative embodiment, stimulation is only delivered to the SAFN of both the left and right leg by neurostimulators 51 a,51 b.

Although a neurostimulator 51 b and its associated lead set 86 can be designed to provide stimulation of two or more stimulators 28 (as shown for the system 10 of FIG. 1), there may be manufacturing and regulatory advantages to use a neurostimulator design that has already been approved by regulatory agencies for stimulation of a single site on one leg and also factors related to patient comfort. Additionally, using neurostimulators that have hardware, software, and protocols designed for stimulation of a single site may be easier than designing a more complicated stimulator and user interface to stimulate more than one nerve target using a single stimulator. For at least these reasons, the system 8 can use neurostimulator embodiments that provide for joint operation of, and/or connection between, two or more neurostimulators.

When two neurostimulators 51 a, 51 b use a pay-per-use, or pay-per-therapy-session, or other treatment-credit-based system, then a therapy protocol which includes stimulating two different targets in single patient may require certain features to avoid problems that would otherwise occur. For example, although two stimulators are being used during a single treatment, it may not be desirable or appropriate to charge for two different treatments and decrement the treatment credits by 2 rather than 1. Several solutions are provided by the systems and methods disclosed herein. In an embodiment a user/physician programmer 70 may communicate in a wired or wireless manner with the payments and permissions modules 202 of the first and second neurostimulators 51 a, 51 b such that both neurostimulators can be activated to provide a treatment but only one neurostimulator will have its treatment credit value decreased. In the figure the neurostimulator on the right side of the figure has had its credit reduced by 1, to 15, while the neurostimulator on the left remains at 16 credits during the provision of the current treatment. Alternatively, the user/physician programmer 70 may be responsible for management of the treatment credits and can send activation codes to the neurostimulators 51 a, 51 b which simply obtain permission from the user/physician programmer 70 to operate to provide treatment. Alternatively, one of the first and second neurostimulators 51 a, 51 b is designated a ‘Master’ device while the other is designated a ‘slave’. The designation can be implemented using either hardware or software or both, and may be realized as part of the payments and permissions module 202. For example, the master device keeps track of the payment credits and the slave device is controlled by the master device, and may not be used or controlled in the absence of the master device. In an alternative embodiment, a high frequency low amplitude signal can be transmitted by one stimulator and must be sensed by a second stimulator in order to ensure the two stimulators are attached to the same person. The signal can be transmitted and received wirelessly using near range communication by the communication modules 68, or can be transmitted by one stimulator 51 a through the patient tissue and sensed by the other stimulator 51 b, whose sensing module 55 is configured to detect this signal. Using a treatment credit system for payment may be more easily applied to stimulation of 2 or more sites since using a needle stimulator with a fuse may double the cost of treatment when 2 sites are used.

In embodiments, various limitations may be imposed by the payments and permissions module 202 to deter fraudulent treatment of two patients while only being charged for 1 treatment. For example, both stimulators can be simultaneously activated to provide therapy, but an operation limitation requires that the start of therapy must occur within 5 minutes of a communication session with the user/physician programmer 70 for both a first and second neurostimulator 51 a, 51 b. Alternatively, the first and second stimulators 51 a, 51 b can be required to periodically attempt communication with each other during the provision of a therapy session and if this is not successful (e.g., for at least 1 of 4 attempts) then it may suggest that the devices are being used in 2 different locations with 2 different patients. If this requirement was not met, then the system 8 can be designed so that the “activation” of at least one of the two neurostimulators is halted so that it does not provide therapy or an alert signal is sent indicating that the two devices are not communicating correctly. Wired or wireless communication can be provided by the communication modules 68 of the neurostimulators, and also of the programmer 70. A near field wireless technology can be used to establish a communication channel that allows for approximately only, for example, a 1 to 2 foot range for communication in order to ensure that the two neurostimulators are in close proximity. Additionally, a conduit 90 such as a microUSB, or custom, cable can be inserted into one of the I/O ports 114 a of each neurostimulator, and the two neurostimulators can communicate in a wired manner to allow the therapy to be delivered using the appropriate allocation of a single treatment credit.

The neurostimulators 51 a, 51 b and a user/physician programmer 70 (which is a device such as a computer having controller circuitry such as a processor, display, memory, power source, communication means, and other circuitry as is well known) can communicate to transmit data and/or power signals to each other. The user/physician programmer 70 can, in turn communicate with a remote management computer 71, and can relay communication between other system 8 components. The management computer 71 may be at least one computer, or part of a network of computers that operate software instructions under control of their processors to manage aspects of the therapy such as purchase and delivery of payment credits and/or recording, assessing, and reporting data related to times and durations when therapy was provided. The management computer 71 is able to set flags and operational values related to use, payment, and compliance, as well as other relevant data. In an embodiment the user/physician programmer 70 can communicate with a remote management computer 71 to transmit a signal over a computer network to submit a request for one or more treatment credits with associated reimbursement codes that are related to providing stimulation using either one neurostimulator or more than one neurostimulator (or one stimulator which is being used to treat one or more sites). In the latter case, in an embodiment, the remote management computer 71 can provide the user/physician programmer 70 with therapy credit that is designed to allow for the activation of two neurostimulators to be used in treatment of a single subject. In additional embodiments, rather than one or more neurostimulators keeping track of the therapy credits, the user/physician computer 70 can manage the treatment credit usage. For example, the user/physician computer 70 can provide an activation code signal to the two or more neurostimulators and then operate its processor to decrease the treatment credit value stored in its own payments and permissions module. For tracking purposes each treatment credit may have a unique ID value. The ID value may contain fields for information about when, where, and how the credit was purchased and/or used. The ID value accordingly may have a plurality of fields, some of which are modifiable by a programmer or neurostimulator.

When the neurostimulators 51 a, 51 b are used in the setting of a patient's home, or are otherwise used outside of a clinic by the patient, to provide therapy stimulation then the user/physician programmer 70 can communicate with the neurostimulators 51 a, 51 b as well as directly with a remote management computer 71 that manages aspects of the therapy. This is true regardless of whether the therapy is at least one of: transcutaneous (e.g., via electrical, vibratory, magnetic, or other modality), occurs under control of an external device that provides control and/or power of an implantable device that provides therapy, occurs by the programmer 70 communicating with an implantable device to adjust the operations relate to therapy, or otherwise. Additionally, the user/physician programmer 70 in a patient's home may communicate with a remote physician programmer 70′ at the patient's physician's office which may, in turn communicate with the remote management computer 71 in order to manage the patient's therapy. In other words, the physician programmer 70′ at the physician's office can act as a relay between the user/physician programmer 70 at the patient's home and the management computer 71. The management computer 71 may be operated by a medical company that charges users or doctors for ongoing use, per-treatment use, time-based rental, purchase, and/or periodic activation of the neurostimulators for selected intervals of time (e.g. 1 hour or 1 month). The management computer 71 may in turn send and receive information with computers of insurance companies in order to carry out operations related to insurance monitoring and reimbursement. Rather than a user programmer 70 communicating directly with a medical company or insurer, a clinic may prefer the user programmer 70 to communicate with the physician programmer 70′ at the clinic, which in turn communicates with the management computer 71. This indirect route of sending data over a computer network, by routing information through the clinic may be preferable for the clinic (who may wish to charge or monitor user treatment) and also for a medical company that may choose not to directly communicate with or receive data from patient devices. Additionally, during a periodic exchange of data related to device payment, data relating to device use (stimulation times, durations, and stimulation parameters) can be exchanged. The transmission of user data from user devices to a physician programmer 70′ may provide a doctor with the opportunity to review the usage of a particular patient rather than requiring this information to be acquired during a patient visit. In some instances, this may reduce the need for more frequent patient visits. In an embodiment, user compliance data (e.g. whether a patient successfully self-stimulated at least a minimum number treatment sessions per week) can be at least periodically communicated with either a doctor's office or an insurance company or both.

When a needle is used to percutaneously stimulate the saphenous nerve it may use a conductive tip that is below a non-conductive region to avoid stimulating near the surface of the skin which may cause pain. In an embodiment, a pulse generator of a stimulation module 54 of the neurostimulator 50 is electrically coupled to both an electrode TENS pad 88 and a percutaneously inserted needle electrode 28 b for stimulating the SAFN. During stimulation treatment, current pulses of the stimulation signal traverse the stimulation site by passing from the TENS electrode 88 to the conductive portion of the needle electrode 28 b. Additionally, the subject system can be configured to operate a needle stimulator with two contacts (e.g., conductive annular rings) formed on an insulated needle that serves as a bipolar electrode. In an embodiment, two conduits can connect to two contacts on the top of the needle stimulator which respectively connect to the first and second annular ring. The needle does not need to be conductive and can be made of plastic or other suitable non-conductive material that has electrical routing disposed along its length provided by conduit means. When two needle electrodes are used, the current pulses can between the TENS electrode and both needle electrodes 28 a, 28 b. In some stimulation protocols, the TENS electrode 88 and the needle electrodes 28 a, 28 b are designated as anode and cathode, respectively, while in others these designations change over time. In an embodiment, the TENS electrode is not used, and the current pulses can travel between the two needles 28 a, 28 b.

FIG. 3a shows an embodiment of neurostimulation system 8 applied so as to stimulate a first and a second target in the same foot of a patient 6. A first and second neurostimulator 51 b, 51 a are configured to provide stimulation to the SAFN using needle stimulator 28 b and PTN using needle stimulator 28 a. A disposable TENS electrode 88 a is attached to the bottom surface of neurostimulator 51 b in order to complete the stimulation circuit with needle stimulators 28 b, 28 a. There may not be sufficient surface area on the medial side of a patient's foot for a both stimulators to be attached. Further due to patient comfort, or for other reasons, it is not preferable for the second neurostimulator to be placed elsewhere on the patient. Accordingly, a neurostimulation linking system can be realized using a communication cable 90 which connects to I/O connectors 114 a provided in the housing 12 of each neurostimulator (see FIG. 2). In an embodiment, I/O connectors 114 a connect to various components of the neurostimulators 51 b, 51 a including a circuit 145 (see FIG. 9) that electrically joins the circuitry of the stimulation module that connects to the TENS electrode used for the neurostimulator 51 a, to the electronics connected to the TENS electrode 88 a of neurostimulator 51 b. This allows the disposable TENS electrode 88 a of the first neurostimulator to serve as the return path for the second neurostimulator as well. The neurostimulation linking system can also be designed to enable data signals sent using wires of the communication cable 90 such as those related to the operation of the payments and permissions modules 202 of both neurostimulators. Communication cable 90 enable the modules of the two systems to collaborate to provide stimulation while managing treatment credits appropriately (e.g., decrementing the treatment credits of only 1 of the neurostimulators due to the provision of a single therapy session).

An alternative system and method of connecting the two neurostimulators, which also does not require the second neurostimulator to be attached to the patient's foot, is shown in FIG. 3b as a TENS electrode linking system. In this example embodiment, two disposable TENS electrode pads can be attached via their electrically conductive snaps 89 a,89 b to the bottom of the two neurostimulators 51 a, 51 b as would typically be done when providing therapy to a patient. The first TENS electrode pad 88 b has a bottom side that makes contact with the patient's skin and a top side that snaps onto the first neurostimulator 51 b to provide electrical connection from the neurostimulator to the patients skin. The first TENS electrode pad 88 b also has a connector for connecting to a second TENS electrode via a linking cable 91. The second neurostimulator 51 a also has a TENS electrode pad 88 a that can then be electrically and physically connected to the first TENS electrode pad 88 b by a linking cable 91. In this embodiment, the second TENS electrode pad 88 a is not attached to the patient and therefore does not require its bottom surface to be adhesive or electrically conductive, although it can be. In an embodiment, the second TENS electrode pad 88 a is realized simply as a snap-type connector that snaps to the bottom of the neurostimulator 51 a and connects to cable 91. Alternatively, when only one neurostimulator 51 b is used, it may be designed to connect to electrode pad 88 b to provide stimulation to a patient's skin, and may have 2 stimulation channels for stimulating at 2 different needle electrode sites, both of which are commonly referenced to the pad 88 b.

FIG. 4 shows an embodiment of a neurostimulation system applied to a leg of a patient 6 for providing percutaneous stimulation. The neurostimulator may be configured to provide stimulation of the SAFN using needle stimulator 28 b at a first location near the knee—at a position 2-3 inches distal to the knee and on the medial surface is shown. More specifically, the SAFN can be targeted by inserting a 34 G needle electrode within a ‘notch’ region located between the medial condyle of the tibia and the superior border of the medial gastrocnemius muscle. It is oriented in the anterior-posterior direction and has a width of approximately 1.5 cm. In over 20 patients the notch was recently found by the inventors to easily and quickly provide a site for successfully stimulating the SAFN using percutaneous stimulation, with patient confirmation of SAFN stimulation achieved when the sensed an electrotactile stimulation was experienced as radiating towards, and even into, their foot (MacDiarmid, Yoo and John, Percutaneous Saphenous Nerve Stimulation: A New Technique in the Treatment of Overactive Bladder, In Prep, incorporated by reference here). Further in this study we found a robust treatment response with patients showing improvement which appears stronger than that typically seen with tibial nerve stimulation. In a system and method of the current invention, users are instructed to use this area to provide stimulation. Additionally, or alternatively, PTN stimulation may be provided using needle stimulator 28 c at a second location cephalad and posterior to the medial malleolus to stimulate the PTN. A TENS electrode 88 placed on the medial aspect of the foot (or between the two electrodes, near the tibia at about the level of mid-calf, not shown) may be used to complete the stimulation circuit in the case where one or more needle stimulators are used. Alternatively, the stimulation pathway may be defined simply using the first and second needle electrodes 28 b,28 c. Additionally, the first needle electrode and the TENS electrode near the calf may be define one circuit and the second needle electrode 28 c and the electrode 88 may define a second stimulation circuit. Stimulation of the SAFN using a needle electrode near the knee has been previously used to provide electrical-nerve stimulation for target site validation when providing lidocaine nerve block of the foot (Benzon et al. Comparison of the different approaches to saphenous nerve block. Anesthesiology. 2005 March; 102(3):633-8). Accordingly, methods for determining the location of the SAFN have been successfully practiced using imaging modalities such as fluoroscopy, ultrasound, and/or electrical stimulation techniques, which can also be incorporated into the currently disclosed therapy for overactive bladder or other disorder. Typically, however, subjective responses such as the feeling of tingling being reported by a subject (SAFN) can be used to select and confirm appropriate target locations for providing therapy. For the PTN the observation of motor evoked muscle activity can be used to select and confirm appropriate target locations for providing therapy. SAFN and PTN targets should be confirmed and stimulation parameters set up separately prior to providing therapy. Further, a method for determining correct placement of an implanted device may include assessing candidate locations using percutaneous stimulation. The site producing highest tingling or the lowest threshold of amplitude at which tingling is detected maybe as suitable site for implant.

Rather than stimulating both the SAFN and PTN, stimulation can occur at two or more different locations along the SAFN and its branches as a means of increasing the therapeutic effects. One needle electrode can target the SAFN trunk (28 b) while the second needle electrode 28 c can target a different area of the SAFN trunk at a location about halfway between the knee and medial malleolus or the anterior SAFN branch located cephalad and anterior to the medial malleolus. The second needle electrode 28 c can also be positioned to stimulate the posterior SAFN branch (and/or the PTN) at a location cephalad and posterior to the medial malleolus, although determining co-activation may be difficult due to motor activity. Alternatively, the second needle can be located above the first and can target the infrapatellar branch or other SAFN target above, at, or below the level of the knee. The method of FIG. 13A can be used to position the needle electrodes when providing stimulation at two or more stimulation sites.

As the inventors have described previously (see U.S. Pat. No. 9,610,442), due to the different profile (i.e., frequency response curves) produced when rat SAFN and PTN nerve targets were stimulated, as well as the different spinal projections, it may be that the bladder reflex circuits of the SAFN and PTN are at least partially independent. Accordingly, rather than stimulating only the SAFN, additional improvement may be obtained when stimulating both the SAFN and PTN as part of treatment. It is also worthwhile noting that the acute and prolonged responses to bladder stimulation were different and suggest that individual patients may receive greater benefit when using SAFN relative to PTN (although potentially the opposite may be true in some patients), to treat acute urge incontinence symptoms, while greater prolonged response may be obtained when stimulating the other target.

FIG. 5 shows an embodiment of a neurostimulation system applied to a leg of a patient 6 for providing TENS of the SAFN. The neurostimulator 50 may be configured to provide stimulation of the SAFN at a first TENS stimulator 30 b at a location on the medial aspect of the leg near the knee, and/or a second TENS stimulator 30 c at a location cephalad and anterior to the medial malleolus, and/or a third TENS stimulator 30 d placed at a location midway between the locations of stimulators 30 b and 30 c (and also which may typically be positioned closer to the tibia to lessen concurrent simulation of calf muscles). A TENS electrode 88 can also be placed on the medial aspect of the foot in order to complete the stimulation circuit or pairs of electrodes on the leg may serve to provide two independent stimulation signals (e.g. between 30 b and 30 d, and between 30 c and 88). Alternatively, the stimulation protocol may provide stimulation with a circuit that may only include two electrodes located in approximately the shaded medial region of the leg “medial target region”. In an embodiment, additional TENS stimulators may be used along the medial aspect of the leg starting approximately at the level of the knee in order to stimulate the SAFN. Electrodes can be positioned above the knee or on the lateral surface of the leg, but these may stimulate the sural nerve or other targets rather than the SAFN. If electrodes are placed on both the lateral and medial aspect of the leg, the stimulation pain threshold may be lower for the lateral site. In some people, this may limit the stimulation level that is able to be provided to the medial target.

The TENS stimulators on the leg 30 b, 30 c, 30 d may be anode, and the TENS electrode on the foot 88 being a cathode (or vice versa), or this status can change with the characteristic of the pulses of the stimulation signal. Only two TENS electrodes on the leg may be used to provide stimulation. Alternative configurations for TENS electrodes (e.g. bipolar pairs, different sizes of TENS electrodes that change the current density, etc) are well known, have been described in the prior art related to providing TENS stimulation, and can be used with the claimed system.

In embodiments, any of the TENS electrodes 30 a, 30 b, 30 c, can also be allocated to serve as a patient ground or be used to measure electrode impedance or nerve/muscle activity before or during stimulation treatment (e.g., between stimulation intervals).

SAFN stimulation using TENS with electrodes located at approximate positions 30 b and 30 d in the figure has been used to provide electrical stimulation of the SAFN in a study conducted by one of the inventors pilot results collected in healthy control subjects who did not suffer from bladder disorders such as OAB, showed that 15 out of 15 subjects (100%) were able to report a cutaneous sensation of tingling (paresthesia) radiating down their lower leg during stimulation (Eshani, Hunter, Hassouna, and Yoo, Investigating the Feasibility of Non-Invasive Peripheral Nerve Stimulation for Treating Overactive Bladder, In Prep.). Most participants indicated paresthesia down to the level of the medial malleolus, while some subjects indicated that paresthesia extended to their hallux. FIG. 6B. shows shaded anatomical plot of the sensation perceived during SAFN stimulation, showing that as the amplitude was increased from threshold skin (Tskin) to threshold where discomfort was experienced (Tlimit), the evoked sensation spread from under the positions of the electrodes across the entire medial aspect of the lower leg, down to the ankle or hallux reflecting recruitment of the SAFN (N=15 subjects, but key=14 since there was not common overlap of sensation across subjects). These results suggest, for the first time in humans, that the SAFN trunk could be successfully activated by external TENS stimulators (which were oriented vertically and positioned medially on the upper leg), below stimulation amplitudes that can cause discomfort or pain to the subject. Furthermore, in a subject who did not detect this sensation at the initial stimulation location, moving the TENS electrode to a second target site and trying again resulted in positive electrical recruitment of the SAFN at stimulation levels below pain. Review of individual data suggested that while sensory recruitment threshold was lower than nerve recruitment threshold, and both of these were lower than pain threshold, it was not possible to predict one threshold from knowing the other (i.e. nerve recruitment threshold could not be easily used to accurately predict pain threshold). These results support that TENS-based SAFN stimulation at targets selected between the knee and cephalad to the medial malleolus are easily found and may be effective in the treatment of OAB.

Although the maximum amplitude tolerated by participants in this study ranged from approximately 20 mA to 60 mA, other stimulation parameters (such as frequencies between 2 Hz and 50 Hz, or stimulation duration between 15 minutes to several hours) may have different maxima and may be assessed, selected, and then used in patients during therapy, or changed as therapy progresses. In embodiments, the stimulation waveforms can be a carrier waveform with frequency in the kHz range, such as a 5,000 Hz-50,000 Hz (or higher), that is modulated by an activation signal delivered at 5 to 20 Hz. Additionally, other characteristics such as amount of body fat, edema, impedance of skin, and conditions such as diabetes that affects sensitivity to pain may require adjustments in the stimulation waveforms or sites used during therapy for individual subjects, and may be perceived differently than (or not perceived at all such as in the case of some diabetic patients or patients with other medical problems) the stimulation waveforms used in the above study in healthy, young subjects. Additional therapeutic benefit may be obtained by providing the TENS stimulation bilaterally in either a concurrent or alternating manner, with respect to a single treatment session or across individual treatments. Additionally, since the SAFN has been used to successfully produce paresthesia, TENS based stimulation may be used to decrease discomfort associated with foot pain as well as provide treatment in OAB. In an embodiment the maximum amplitude provided by a TENS neurostimulator may range from 100 mA to 200 mA.

Percutaneous TN stimulation therapy treatment sessions typically occur for about 30 minutes once per week during an induction phase, and once per month during a maintenance phase. In contrast, during treatment with TENS in a home setting, subjects may provide SAFN stimulation for at least 30 minutes every day, every other day, or at least once per week during induction. This can occur just as frequently or less frequently, for continued benefit during maintenance. Therapy may also include providing TENS during sleep for least one night per week. Especially during long (e.g. >1 hour) therapy periods, the neurostimulator 50 may realize a stimulation protocol that provides intervals of non-stimulation between the stimulation intervals, for example, 30 minutes on, then 2 hours off, then 30 minutes on, etc. This may provide advantages of both less skin irritation and can also extend periods between recharging or decrease the size of a battery.

The neurostimulator 50 can be programmed with various “SLEEP” protocols and features. These can be selected by a patient at bedtime or be prompted or selected automatically by the system as a function of clock-time. The SLEEP protocol can cause the neurostimulator 50 to gradually increase to a selected therapy amplitude across a period of 1 hour, and/or delay onset by 1 hour, in order to decrease the risk of interfering with a subject's sleep. The protocol may also cause the stimulation amplitude to gradually ramp down after an interval that is defined to end an hour or so prior to when the subject is expected to wake up in order to deter early awaking. If the system is provided with, or is in communication with, a sensor (e.g. EEG, EKG, strain, or accelerometer sensor), and a processor is provided in a sensing module 55 that is able to algorithmically assess arousal level, sleep, or sleep stage based upon sensed data, then TENS stimulation may only occur when evaluation of sensed data meet a selected criterion. For example, stimulation may only be provided during certain sleep/arousal stages or only when the subject is experiencing restful sleep (e.g., leg movement measures remain below a selected threshold). A stimulation protocol that is defined for providing stimulation for longer periods (e.g. several hours at night) can use different stimulation signals than those used during a 30 minute therapy session, For example, the amplitude of the signals may be lower those used for 30 minute sessions.

Patient Safety Across Stimulation Type.

Stimulation signal amplitudes may be lower when the neurostimulator 50 uses needle electrodes rather than TENS electrodes. Accordingly, in order to provide for patient safety and deter unwanted or unintended stimulation signals from being erroneously used, a number of hardware and/or software safeguards can be used. For example, a lead set 24 that is attached to the device by plug 22 uses a lead set or plug for providing TENS stimulation that is different, and may even connect differently to the system, than that which is used to provide percutaneous stimulation. Additionally, these two different types of lead sets/plugs can contain circuitry that adjusts the amplitude of the stimulation signal output by the device 50 so that it is appropriate to the therapy being delivered to the patient. The neurostimulator may allow users to toggle the control module 52 to operate in a percutaneous mode or TENS mode. Each mode has a set of one or more stimulation protocol parameters that create stimulation waveforms that are appropriate for the two different types of stimulators (e.g., voltage, current, pulse-width, or duty cycle). However, for safety or other reasons it may be preferable to use two different lead sets that inhibit a user from accidentally providing a stimulation signal that is higher or lower than what is intended. The plug 22, can also communicate, or otherwise operate in conjunction with, internal modules of the device in order to adjust the amplitude, or maximum amplitude that is permitted while the plug is attached to the housing 12. In an additional embodiment two different plug+lead sets can be used, where the plug that is used during TENS stimulation fits a first connector of the system and a different shaped plug fits a second connector of the system. In an additional embodiment an adaptor can be provided for a plug that is used during percutaneous needle stimulation that fits a first connector of the system (and attenuates the stimulation signal by a selected amount) and the plug for the TENS lead set can be attached directly to a connector of the system 10. The lead sets used for percutaneous stimulation may have circuitry that attenuates the strength (e.g., voltage, current, pulse width) of the stimulation signal output from the device 50, while the TENS lead set does not have this additional circuitry. Alternative methods for providing patient safety are disclosed later in this specification.

FIG. 6A shows an embodiment in which TENS stimulators are applied to the back of a patient in order to stimulate either lumbar and/or the combination of lumbar and sacral nerves. Current investigations of sacral stimulation therapy using TENS (e.g. ClinicalTrials.gov Identifier: NCT01940367) instructed subjects to place surface electrodes, 2″×2″ in diameter, over sacral foramen S2-4, bilaterally, using 2 channels (4 electrodes total). Approximate locations are over posterior superior iliac spine and inferior lateral angle of sacrum. As is shown in FIG. 6A, using TENS electrodes more cephalad to the locations used to stimulate sacral targets 36, such as locations 34 over the lumbar sites L2-L5 can be used instead of, or in addition to, the currently evaluated approach to provide improved therapy. During the provision of therapy, stimulation may be provided using different patterns. For example, stimulation can be sequentially applied to contralateral electrode pairs (at the same level of the spine) rather than concurrently (e.g. L2 left and L2 right, then L4 left and L4 right), or ipsilaterally (e.g., L2 and L4 left, then L2 and L4 right), or can be applied to single targets (e.g., L2 left with an electrode placed on the patient's thigh to close the circuit). Additionally, in an embodiment, treatment using the lumbar TENS sites can be used in patients who do not respond to stimulation of other targets such as at sacral target sites.

Patient Compliance

In a trial, or clinic-based, setting the detection of non-compliance may allow for corrective measures and interventions that can ultimately cause therapy to be successful rather than fail. When providing stimulation at home, rather than in a clinic, monitoring and promoting patient compliance can be essential. Especially in more severe cases of OAB, an increased amount of stimulation may be needed in order to obtain therapeutic benefit, rather than 30 minutes once or twice a week. Patient compliance may be a challenge both for TENS, magnetic stimulators (e.g. TMS devices) and for ‘implantable’ therapies that are powered by, or controlled by, external components of the neurostimulation system. In therapy systems that stimulate targets such as the PTN or SAFN and do not provide for an internal battery in implanted components, the patient must remember to activate an external controller in order to activate the implanted neurostimulator. The provision of a compliance module 200 is important because it is well known that patients can be inaccurate about their actual compliance, and this can be a greater concern for older OAB patients. It may be important for a doctor to be able to accurately assess patient compliance, rather than simply the reported compliance, in order to determine if a patient is not responding to therapy due to compliance issues or due to other reason such as lack of a treatment response in a compliant patient. Accurately tracking compliance may also be important in assessing efficacy in clinical trials where subjects are expected to provide self-stimulation outside of a controlled setting.

In embodiments of the current invention the user/physician programmer works with an implantable neurostimulator. An example the Stimguard or Bluewind systems which are undergoing clinical trials and another is eTENS, which we have previously described. It is typically not useful for a doctor to assess patient compliance in self-stimulation during a clinic visit by patient report which may not be accurate. Existing TENS systems do not allow a doctor to assess patient compliance outside of their clinic visits using remote monitoring. Accordingly the subject invention is provided with functional modules that address current limitations related to managing and augmenting patient compliance.

In an embodiment, a compliance module 200 is realized within at least one component of the system 8 such as the neurostimulator 50, and/or the user/physician programmer 70, and/or the management computer 71, and performs operations related to patient compliance. The compliance module 200 can operate, and work with the other modules of the neurostimulation system, in order to manage, monitor, track, promote, summarize, analyze, display, report, transmit, process, and alert to, aspects of patient compliance (Give an example of each of these including sending to a doctor). Although existing TENS units can monitor patient usage in the form of total treatment time provided (e.g., in total hours) since the reset of a counter, there is no provision for many other characteristics related to patient compliance. The compliance module 200 stores a detailed historical record of patient use and displays the actual usage using metrics that reflect a per-hour, per-day, or per-week basis. Some additional features and advantages of the compliance module 200 of the present invention, that address limitations of the use-counters of existing TENS devices are now further disclosed.

The compliance module 200 can alert a patient 6 by operating the user interface module 80 or communication module 68 to provide an alert signal to a patient about a scheduled therapy interval. The alert signal may be communicated from a device of the system 8 to a patient's smartphone or may be realized as a sonic or visual alert provided by the user/physician programmer 70. The alerts may be used to alert the patient (or physician or other intended recipient) to compliance failures when a compliance criterion is not met. A compliance failure may occur if a patient fails to provide stimulation for one or more scheduled therapy sessions within a defined time interval (e.g. within 24 hours after stimulation was supposed to occur), or in response to failing to meet other compliance conditions as will be disclosed. The compliance module 200 can also alert a user to the approach of a scheduled stimulation session/time.

In embodiments, compliance module functions can be realized, at least in part, by a customized application operated on a patient's smartphone. For example, an application running on a processor of a smartphone according to instructions provided on computer readable media can cause an alert signal to be issued to a patient or caregiver to remind about a scheduled therapy. The alert can be set to occur prior to a scheduled therapy time (as a prompt), or at a selected time after the therapy if the patient did not provide correct or insufficient therapy (as a reminder), or both.

A smartphone-based compliance application can be considered as one alternative embodiment of the compliance module 200, and may be operated independently or in combination with the compliance module 200 of the system. A smartphone compliance application that does not communicate and cooperate with the compliance module 200 of the neurostimulator may be limited and may simply serve as a reminder-system, since while the application provides reminders to a patient it may not be able to monitor and/or determine if therapy is provided by the system 8. However, an integrated system is preferred and wireless communication between the neurostimulator 50 and a patient's smartphone can occur via radiofrequency, Bluetooth, sonic, infrared, WIFI, or other one-way or two-way communication protocol.

FIGS. 7A and 7B show two embodiments of compliance screens that can be provided using information generated by, stored, and operated upon by the compliance module 200. FIG. 7A shows a month-calendar summary view that displays both total therapy per week (in minutes) as well as maximum and minimum durations during which individual therapy sessions occurred. The weekly summary statistics are presented in the therapy summary table on the left hand side of the screen and include total minutes per week, and the minimum and maximum durations for stimulation sessions provided by the system. Also shown in the bottom row of summary statistics is the integrated time across the entire month, which provides a simple patient compliance measure that shows the total treatment time in hours.

There may be different compliance criteria that must be met in order for the patient to be considered compliant. For example, a monthly therapy compliance criterion may require that at least 2000 minutes of therapy be provided each month. In this example, the patient has met this criterion successfully (i.e. the patient provided 2157 minutes). Alternatively, a weekly therapy compliance criterion may include providing therapy for at least 120 minutes per week. In this case the patient did not meet this therapy compliance criterion in the 3^(rd) full week of April where only 60 minutes of therapy were provided. The compliance failure is reported by a shaded value of “60”. A therapy criterion can also exist for a time of day, for example a therapy criterion can require a patient to have at least 3 sleep/night sessions of at least 5 hours each week. Therapy compliance criteria as well as contingent actions which occur if one or more criteria are not met can be selected or adjusted by a user such as a doctor, caretaker, or patient. A password or other permission schema may be used to restrict access to the operations that allow therapy criteria to be adjusted. Additionally, summary statistics can be calculated and displayed by the compliance module 200 that compare the times and durations a patient provided therapy in relation to pre-set treatment schedules. Therapy compliance criteria can be set for minimum/maximum durations, stimulation amplitudes to be used during treatment, and other characteristics.

FIG. 7B is an alternative view of compliance data monitored, stored, and summarized and displayed by the compliance module 200 which in this example is shown in a weekly view that also shows the hours of each day of week that therapy was provided. This view can be obtained by a patient (or doctor) by clicking on any week of the calendar shown in FIG. 7A. Night time data (times when the patient is typically sleeping or as determined by analysis of sensed data such as accelerometer data) can be shaded in one color (e.g., grey boxes), and times when the patient is typically awake can be shaded in a different color such as white.

Either an implanted neurostimulator or an associated external device that provides power/data signals to control therapy can operate a compliance module 200 to generate and log in device memory a record of operation. It can further compare use information to compliance criteria to monitor, generate and store a log related to, assess, transmit, promote, alert to and display compliance or lack of compliance.

The compliance module 200 can monitor and assess a patient's compliance using various compliance criteria, such as the following:

A daily compliance criterion can include a minimum amount of time per day during which therapy must be provided, for example, at least 30 minutes of approximately continuous stimulation, using a minimum amplitude, on a given day.

A nightly compliance criterion can include a minimum amount of time per night during which therapy must be provided, for example, at least 6 hours on a given night.

A weekly compliance criterion can include a minimum amount of time during the week during which therapy must be provided, for example, at least 20 hours per week. Additionally, a weekly compliance criterion can include meeting the daily compliance criterion for at least a selected number of days (such as 3 days of the week). A weekly compliance criterion can also require for example, at least 3 days of therapy and further require that a day with no-therapy occurs between each day of therapy. A weekly compliance criterion can also require, for example, that the daily compliance criterion is met at least twice over the course of a week and the night criterion is met at least once.

A monthly compliance criterion can include a minimum amount of time during the month during which therapy must be provided, and may include additional compliance criteria such as that at least 2 of the 4 weeks must be weeks where a weekly compliance criterion was met.

Compliance criteria can relate to stimulation protocols rather than number of treatments or total therapy duration. For example, a compliance criterion may require such characteristics as stimulating both legs instead of one leg at least once a week. A compliance criterion can require a patient fill out an electronic bladder diary, a quality of life survey, or provide responses to Likert-type scales that are provided by a device of the system 8 according to a schedule such as at least once every two weeks. A compliance criterion can require that more frequent stimulations such as every other day are provided at the beginning of therapy and after an interval such as one month, can then be decreased to require a less frequent schedule of stimulation sessions to be provided by the user. Compliance criteria can also relate to users who take medication and can be calculated based upon user input queries about whether they have taken their medication. Accordingly, stimulation+medication compliance criteria can be operated upon by the system.

Similarly the system 10 may be programmed with a stimulation program that is more frequent in the first days or weeks of therapy, and then this becomes less frequent only if the patient reports benefit in relation to patient input such as responses to survey items provided by the user interface module 80. Additionally, the system may query the patient under control of the patient survey module 61 about symptoms and can begin to decrement the frequency of the treatments after a minimum amount of time (e.g. 4 weeks) if the patient responses rating scales or answers to surveys presented to the user are operated upon and determined to show improvement (e.g. QOL scores improve over a selected amount). The patient alerting and compliance module 200 parameter values can then be adjusted accordingly.

In addition, compliance may relate to enforcement of compliance restrictions. For example, the compliance module may dictate that a patient cannot provide therapy more than a certain number of times per-day or other interval. The restriction can be assessed by comparing usage to interval rules. Further the restriction can be a combination of both time and treatment strength and assessed using interval-strength rules. For example, a patient who uses larger stimulation amplitude may be restricted to a lower number of maximum treatments within a selected time interval. Unlike medication, where a patient ingests a certain number of pills over the course of a defined interval and must obtain refills at the end of the interval, there may be no evidence of patient over or under usage of electrical therapy in the absence of the compliance module 200.

The compliance module 200 allows doctors or patients to adjust how compliance is managed by selecting what the compliance criteria are for an individual as well as how and when the therapy schedule may change over time. Both usage and compliance can be tracked over time, and this can be displayed to a user or remotely to a doctor. The promotion of compliance can occur with setting reminder alerts to occur before a scheduled stimulation session, or after the time when this was scheduled if it did not occur, etc. Reports related to usage and compliance can be stored and transmitted over computer networks in order to allow for remote patient monitoring and management. The various features should improve patient compliance.

In the case of patient non-compliance various operations may occur according to the compliance module 200 in conjunctions with the other system components and methods of the invention. For example, failure to meet a monthly compliance criterion for X out of Y months, or for a selected number of sequential months, can result in the compliance module 200 causing an alerting module 204 to cause a signal to be provided to the patient or medical care provider. Alternatively, a compliance module 200 algorithm may cause the neurostimulator to deny/restrict stimulation until it receives a reset signal from a remote physician computer 70′. Additionally the patient prescription status flag may be changed to inactive in the remote physician computer 70′. In other words, if a patient is not compliant and then wishes to use a neurostimulator then they may first have to meet with their doctor to discuss the non-compliance and have their device re-enabled. The doctor may need to submit the compliance record of the patient and evidence of a patient visit in order to obtain an approval from an insurance carrier to re-activate a neurostimulator of a patient. This may further be tied to requiring a new prescription be written and prescription status updated in the system.

The compliance module may operate to provide different alerting schemes for treatment of different disorders. For example, if the TENS system is used for providing transcranial direct or alternating stimulation (i.e. tDCS or tACS) in the treatment of depression or anxiety, failure to adhere to a treatment schedule may result in the system communicating with a computer 70,70′ to alert a doctor or caregiver that a patient is not complying with a therapy regimen. Alternatively, if the tDCS/tACS is used to provide cognitive enhancement, then no such notification may occur. In an embodiment, compliance operations relay upon timing circuitry, such as a real-time clock, to calculate times and dates related to when and for how long stimulation was provided.

The payments and permissions module 202 can communicate with a remote a remote management (e.g., a computer of an insurance company) or physician computer 70,70′ in order to ensure that a patient is in good standing before enabling the provision of therapy. For example, a remote management or physician computer may assess whether 1. The patient has met various compliance criteria; 2. The patient has an active prescription for the therapy from their doctor which has an associated “active” status flag that is set in the neurostimulator; 3. Insurance is in good standing; 4. The account associated with the neurostimulator has not been flagged for any reason, such as a) doctor has failed to meet with the patient for too long a time since prior visit b) the neurostimulator is scheduled for calibration/maintenance/replacement or c) the neurostimulator has sent flags related to device operation, faults, failure to meet calibration and/or self-test routines etc.

FIG. 8 shows a neurostimulator device 50 that can be used to realize the methods and systems of the current invention. The neurostimulator 50 is illustrated with a number of modules and components which may be included, omitted, or modified in various embodiments. The modules provide functionality to the neurostimulator and, while shown discretely, may share software and hardware components with each other. Further, each of the modules may be realized within the neurostimulator housing, outside of the housing, or both (i.e. in a distributed manner). Modules may be realized jointly between the neurostimulator 50 and an external device such as a user/physician programmer 70 and can be redundantly provided within different components of the neurostimulation system. For example, an alerting module 204 may be realized within an implantable neurostimulator, an external neurostimulator, a user/physician programmer, and/or a remote management computer (or a computer network of which it is a part).

The device 50 comprises a control module 52 with circuitry for controlling the various other modules of a neurostimulation system 8. For example, under its direction, the stimulation module 54 and sensing module 55 can be controlled according to user input commands and/or treatment protocols and parameters stored in the protocols and parameters module 66. Treatment protocols can include stimulation protocols, sensing protocols, alerting protocols and evaluation protocols. A non-transitory computer-readable medium is provided in the control module that is configured for storing one or more instructions configured to be executed as part of a treatment protocol by at least one processor of the system, which can be at least one processor of an electrical stimulation device 50 or a user/physician controller 70, or a remote physician computer 70′ that communicates over the internet with rest of the system. These protocols may enable the control module 52 of the device 50 to responsively adjust its operation in relation to, for example, the evaluation of sensed data (e.g. accelerometer data) or detection of defined events as provided by the sensing module 55, patient input data managed by the user interface module 80, time intervals assessed by the control module 52, and other triggers that can cause the selection, provision, and adjustment of therapy as defined by the parameter values and algorithms related to a particular treatment protocol. The device 50 can also simply provide stimulation in response to user input when operated by a user.

The control module 52 has a timing module 56 including a real time clock and a timer, a processing module 58 including at least one processor for operating software, and processing information and parameter settings that are stored in memory module 60 and which allow for control of device 50 operation. The real time clock can be used to calculate dates and time to provide event logging and to provide operations related to the compliance module 200. The current date and time can be compared to the date and time of the last stimulation that was provided and the patient can be alerted if a selected amount of time has passed indicating that a treatment is due or has been missed. The time and date can also be used to define and/or realize interval rules which determine, for example, the minimum interval that must occur between subsequent stimulation periods. The date and time can also be used by the payments and permission module 202 to determine if the device is still operating within an interval allowed in relation to payment. The stimulation module 54 can control at least one waveform generator/signal processor such as simulation module 62 that contains circuitry for generating pulses or arbitrary waveforms for output including alternating current (AC) and/or direct current (DC) signals to be used by one or more electrical, magnetic, optical, sonic, ultrasonic or other types of stimulus transducers.

The sensing module 55, may be realized as part of the AD/DA module 64 when AD/DA circuitry (including AC-to-DC, DC-to-AC, and DC-to-DC converters, and allows for both signal generation and acquisition. The sensing module 55 contains circuitry and protocols for conditioning and analyzing sensed data and can also for providing power to, and/or communicating with, various sensors including, for example, position, acceleration, electrical, EMG, optical, sonic, and other sensors that may be used by the system. The processing module 58 enables the assessment of sensed data and can provide detection of events that are defined to cause delivery or adjustment of stimulation. Responsive stimulation may occur in a closed loop manner, via rules or control laws, or may cause information (information about the sensed data) or signals (a flashing light) to be presented to a user of the device 50, such as by an external patient device 72 or physician programmer 70, in order to prompt provision or adjustment of therapy. The processing module 58 may be configured to store data in memory 60 such as historical sensed data records in order to track patient data, or assessment of sensed data along with usage and compliance data.

An AD/DA module 64 allows for conversion of input and output signals as well as amplification, digital signal processing, filtering, conditioning, and also contains safety and regulation circuitry to ensure patient and device safety. The AD/DA module 64 may also contain circuitry for multiplexing signals across different sensors or stimulators, and can contain switches and controllers for routing and controlling electronics of the system.

The apparatus 50 also includes a communication module 68 for providing wired and/or wireless communication with other system components (e.g. RFID identification to communicate between system components) such as a user/physician programmer 70 or management computer 71. The communication module 68 can communicate with a computer at remote medical facility 70′ (to allow data communication and programming to occur remotely) either directly or by way of the user/physician programmer 70. The communication module 68 can provide signals to transceivers which provide one-way or two-way communication of wireless power and/or data signals to implantable components such as neurostimulators. All wired or wireless communication can be realized at least partially using the internet, or a local area network, Communication may also include means for magnetic, radiofrequency (RF), optical, sonic, and/or other modes of data and power communication with other devices. The communication module 68 may include circuitry, hardware, and protocols for providing WiFi, Bluetooth, cellular, magnetic, magnetic inductance, microwave, RF, electrical, optical, sonic, RFID, or other types of communication using communication/interface ports 82, 144. For example, the ports 82, 144 may connect to a system component which provides for wireless communication of data or power signals.

The communication module 68 is configured for use with USB connectors (e.g. 83 c) and the like which may be provided as part of a user interface panel 82. The communication module 68 of the device 50, as well as communication circuitry may operate to send or receive signals using near field, far field, induction, magnetic resonant induction components, coils (e.g. an inductive coil assembly for powering an implantable device), antennae, and/or rectennae, optical sensors and stimulators, sonic stimulators and sensors, etc. This allows for successful communication of identification, data or power signals between any external and internal components of a particular embodiment of the invention. The apparatus 50 also has a power supply/recharge module 74 which can include components such as a battery, AC and DC converters, diodes that function to rectify wireless power signals harnessed by rectennae and circuitry related to the conversion or provision of power which may be related to harvesting or transmission of wireless signals, and can include a power cord for connecting to a wired power source through at least one of the communication/interface ports of panel 82.

The interface ports 83 may be connected to communicate with and/or power various sensors, such as sensors that are configured to measure bladder activity, bladder pressure, bladder fullness, foot twitch, or other characteristic related to a condition or disorder being treated. In an embodiment, urodynamic measurements can be assessed before and after stimulation to determine the effectiveness of a given set of stimulation parameters.

A signal routing module 63 provides components and switches that operate to route signals between components and modules of at least one neurostimulator 50. For example, when a TENS protocol is selected the module 63 may route the stimulation signals to a first connector 22 on the housing of the device 50, while when a percutaneous signal is used then this is routed to a second connector of the device 50. Signal routing may also be used when two or more stimulation targets are stimulated in order to route the signals to the appropriate set of needle electrodes or TENS stimulators. Signal routing may also be used to send signals to a subset of TENs electrodes.

The I/O interface module 75 can contain circuitry and protocols for routing signals and controlling communication related to various input and output ports such as USB or other ports and can further contain safety circuitry and regulators that protect the patient and device 50 from other devices that may be connected to the neurostimulator 50.

The communication module 68 can cooperate with the user interface module 76 which contains hardware and software for presenting information to a user (e.g. patient or physician) and obtaining information/input from the user. Although the device 50 may communicate with a physician or patient programmer 70, or external patient device 72, such as may be realized by a specialized device, smartphone or tablet computer, the device 50 may also have at least one signaling module 78 (which can be part of the alerting module 204) with related circuitry and control a display 79 for presenting visual data in both text and graphical format. This may also be used to present a user with visual alarms related to the provision of therapy and/or to operate a speaker 38 for presenting auditory signals such as instructions to patients related to the therapy (e.g., an instruction may inform a patient that a TENS pad may need to be reapplied because the impedance value is too high). The signaling module 78 can have a Bluetooth enabled sound system that communicates with a speaker 38, or sound transducer such as a hearing aid by way of the communication module 68. The device 50 can also contain patient interface module 80 that permits operation of, and includes, controls such as a keyboard, nobs, switches, etc. to allow a user to provide input. Input can be confirmed by an “enter” button 19. The interface module may also provide for a menu guided system that allows for adjustment of device operation. It is obvious that various modules such as modules 78, 79, and 80 can also be realized within the physician or patient programmer 70,70′.

Both the control module 52 and the waveform generator module 62 may be configured with safety hardware and software routines, and can operate in combination with calibration routines of a calibration module 61 to calibrate the apparatus 50 and to ensure proper functioning In embodiments, the control module 52 allows stimulation programs to be implemented according to protocols stored in the device memory and according parameters that can be adjusted by a user's manual input obtained by the patient interface module 80. The safety routines of the safety module 208 may limit the adjustments made by a user to ranges that are safe.

The interface port panel 82 allows for connection to various system components. The device 50 may use at least a first stimulator conduit 84, a second stimulator conduit 86, to communicate signals to a first stimulator 28 b and second stimulator 88. Conduits can comprise single or multi-stranded electrically conductive, insulated electrode lead wires. The first conduit 84 has a first end connector that may contain a plug that electrically couples to a first stimulator interface port 83 a of the interface 82. When the device 50 is used to provide stimulation using non-TENS modalities the third stimulator interface port 83 c may be configured to be connected to a TMS device to control the provision of magnetic stimulation as part of the system and method of the current invention.

Alternatively, the wired interface port 83 c can allow for connection to sensor components. When the stimulators are TENS electrodes, then these can serve as both stimulator and sensor, typically at different moments in time. Stimulation electrode 88 can serve as sensor when the sensing module (or impedance module) rather than stimulation module is operationally connected to a specific port during a selected period. However, other types of sensors may also be used.

In embodiment the interface port panel 82 may only consist of 1 or two connections that are distributed on the device housing. For example, the neurostimulator 50 can be realized in the form factor shown by neurostimulator 51 a and utilizes a transcutaneous electrode pad such as those commonly used to provide TENS, which may have bottom surface that is an adhesive and conductive surface (for attachment to a patient) and a top surface configured with connector 89 a which may be realized as an adaptor such as a metallic snap to be connected and disconnected to a connector either on the bottom surface of the housing of the neurostimulator 51 a, or to connect to the end of a lead set. The neurostimulator 51 a may have a lead set 86 containing a single lead wire for electrically connecting a single needle electrode 28 b or TENS electrode 88, to the neurostimulator via connector 22. Alternatively, the lead set 86 can contain multiple lead wires for electrically connecting one or two percutaneous needle electrodes, and a TENS pad to the neurostimulator via connector 22.

The alerting module 204 provides functions related to patient alerting and can include providing alerts using sounds emitted by a speaker 38 or visual alert signals provided by displays 79 or communication signals sent using the communication module 68.

The impedance module 206 can provide operations related to ensuring that impedances of the leads used during stimulation are below a threshold level and can provide a user with an alert if the impedance is above this level. This may be important for home users because stimulation will not be effective if the TENS pads do not have good contact with the patient's skin and they may not be well trained to notice bad skin contact.

The patient safety module 208 can provide operations and control hardware related to ensuring patient safety. For example, if the module assesses that a calibration or maintenance date stored in the module has passed it may set a flag and provide a message to a user or may not allow device operation until the flag is reset when the indicated operation is provided. The safety module may also not permit certain operations such as providing patient treatment when the device 50 is connected to a recharging power source.

Payments and Permissions

The payments and permissions module 202 provides for management of device operation. This can include setting what operations and values are permitted to be accessed by a user. Passwords may be required in order to grant access. The module 202 also can allow a user to provide information related to using and purchasing of treatment credits. This can include medical billing information, reimbursement codes, credit card account numbers, user or clinic information and other information related to payments or treatment credits. For example, submission of current procedural terminology “CPT” codes can allow for appropriate coding of the diagnosis using ICD-9 code as determined by the Centers for Medicare and Medicaid Services (CMS) and relate to determination of associated fees for providing stimulation. The reimbursement codes can include whether SAFN or PTN targets are being used and can also indicate if the stimulation protocol being used is for one leg or for both legs. Reimbursement codes used by the system 10 may be country or region specific. Additionally, the payments and permissions can be modified according to region or state. For example, certain states may cover costs related to certain types of stimulation protocols while other states may not and so the operation provided by the system 10 or the type or amount of a charge associated with a particular treatment credit may be adjusted accordingly. Information related to a patient or a patient's insurance may also be used in the processing of the treatment credit information. This can allow the cost for severe or moderate patients, who may need more stimulation sessions, to pay the same amount as patients who need less.

In an embodiment, a neurostimulator 51 a is preferably configured to communicate with a computer system 71 which provides a treatment credit purchasing system and also allows for monitoring the status and usage of a neurostimulator. For example, the neurostimulator 51 a can communicate with the computer system wirelessly or through an input/output connector 144 a which may be realized as a universal serial bus (USB) connector. Information can also be provided to the neurostimulator 51 a using a portable digital storage device such as a USB flash drive. The USB flash drive may allow two way data exchange between the computer system and the neurostimulator or may only be used to update information in the neurostimulator.

If wireless communication not available near a user of a neurostimulator, a user is not technically savvy, or if there are other reasons (e.g. regulatory) why a neurostimulator may not be provided with wireless connectivity, it may be advantageous to provide a physical key, such as a USB memory key. The key may programmed and can be read by the neurostimulator to provide a selected number of treatment credits, or to allow the neurostimulator to operate for a selected amount of time or until a specific date. The USB memory key may fit into an I/O port 144 of the neurostimulator, which can then read the USB key and update its internal parameters. In an embodiment the USB key may be required to be attached to the neurostimulator during use. The USB key and the neurostimulator may be matched 1-to-1, via the payments and permission module 202 which may be programmed to only read a USB key having a particular ID code: the USB key can only be used with a particular neurostimulator. A patient can receive a USB key in the mail and can mail back a previously sent USB key. Alternatively, a patient can be mailed a code that can be manually input by a patient to re-activate the neurostimulator for a duration or to provide additional treatment credits, according to a prescription or otherwise. Alternatively, a smartphone running specialized application software can communicate with a remote computer 71 and the neurostimulator 51 a to manage treatment credits. This allows the neurostimulator to remain relatively simple, and the circuitry and hardware of the smartphone may be relied upon.

In embodiments the neurostimulator 51 a includes a control system 52 with a microcontroller/processor 58 which operates the payments and permission module 202 to manage and store information relating to payment credit status, historical usage, compliance data, and other parameter values of the neurostimulator 51 a. The payment status and usage information may be transferred between the neurostimulator 51 a and the computer system 71 when the neurostimulator is in communication with the computer system 71. The control system 52 monitors the value of a treatment credit counter which indicates a treatment credit value associated with the number of treatment credits that are available.

A treatment credit can correspond to allowing for various types of therapy provision. For example, a treatment credit can be set equal to a treatment session of, for example, 30 minutes of continuous stimulation, and after a treatment session is completed, the number of available treatment credits is decreased by 1. Further, a therapy session may have to be interrupted or paused. Accordingly, in an embodiment a treatment session can have a minimum duration defined before a treatment credit is used, such as 15 minutes. The treatment sessions can also be defined as a selected interval of total provided stimulation (e.g. 30 minutes). The interval may be allowed to occur within a selected interval (2 hours). This can allow for 1 or more interruptions or pauses to occur during treatment. If there are no more treatment credits available to the neurostimulator 51 a, then the processor 58 operates in a manner that prevents the neurostimulator 51 a from providing a session of treatment. For example, this can be done by preventing operation of the stimulation module 54 and also presenting a user with a message or alert using the alerting module 204. In this case, additional treatment credits can be purchased and uploaded into the neurostimulator 51 a to allow for subsequent treatment sessions to occur.

If the neurostimulator 51 a is not used during an interval defined for treatment, or is used less than a minimum selected amount (e.g. 15 minutes) then the payment and permission module 202 of the neurostimulator 51 a can automatically increase the stimulation-credit value by 1 to the prior value. When multiple patients are treated by the neurostimulator the physician can enter the patient ID into either a physician computer or the neurostimulator so that a particular patient is associated with the stimulation session.

In an embodiment, the neurostimulator is permitted to provide stimulation therapy-sessions while the treatment credit value is zero or negative, as long as the stimulation credit value of the neurostimulator is above a defined payment threshold such as −50 units. Further, a treatment credit rule can be implemented by the payments and permissions module 202 of the neurostimulator 51 a, whereby the negative value reflecting a treatment credit deficit must have lasted less than a selected interval such as 90 days. This feature can be important for some clinical practices since a clinic may not be paid or reimbursed for a treatment session until several weeks or months after a treatment is provided to a patient. In this manner, a clinic does not have to pay in advance for credits that may not be used for some indeterminate time in the future.

For various disorders or treatment regimens, a session-based stimulation paradigm may not provide an appropriate unit of therapy. For some patients and disorders more than one session will occur during a particular day. For example, when the neurostimulator 51 a is used for providing treatment related to pain, migraine, headache, sleep apnea, etc., rather than for treatment of overactive bladder, then several treatment sessions can be needed to relieve symptoms. The patient and/or clinic should not be required to use multiple treatment credits. If a treatment credit allows providing only a single session that occurs for a particular day then problem occur. Some patients may worry about cost and try to use less treatment credits rather than providing themselves with additional needed therapy.

Accordingly, in embodiments each treatment credit can enable therapy to be provided multiple times across a selected interval such as a single day, week, or other defined period. Further, the neurostimulator payment and permission module 202 may be configured so that a maximum number (e.g., 10) treatment credits can delivered to a neurostimulator 51 a at a particular time. This provides for an advantage that a patient must contact a doctor or service provider after a period of, for example, two months. Further, although at least one treatment credit is available, the payment and permission module 202 of the neurostimulator 51 a may not allow therapy to be provided in selected circumstances. This may occur if a compliance criterion is not met or, for reasons related to patient safety, a certain number of stimulation sessions, or total stimulation time, may only be allowed to occur within a selected interval such as 1 day.

FIG. 9 shows a block diagram of circuitry modules provided in an embodiment of the neurostimulator 51 a. An graphic display 20 such as an LCD visually presents information related to operation such as neurostimulation parameter values or information about compliance as shown in FIGS. 7A,7B, power levels, elapsed time of stimulation, and treatment credit information. Patient input control can be realized using buttons such as power button 14, dedicated buttons 16 (e.g., start/pause/assess button), navigation controls 18 to assist a user in controlling the operation of device 51 a via the processor/microcontroller 58 of the control module 52. The “assess” button allows the assessment of different stimulation parameters such as amplitude prior to providing therapy. The processor 58 controls operation the stimulation module 54 which includes a high voltage supply (DC to DC converter 154), pulse generating circuitry 140 and presents values of related operational characteristics on the display 20 using control circuitry of the control module 52 including a set of controllers 148. The pulse generating circuitry 140 can also provide circuitry that cooperates with the lead set in order to blow a fuse after the provision of simulation as is done in commercial systems that utilize single use paradigms. The controllers 148 can act as sets of one or more switches or be otherwise realized to adjust and control the operation of components of the stimulation module 54 including, for example, a DC to DC converter module 154, digital-to-analog/analog-to-digital converters 152 under control of the DA/AD circuitry module 64. The controllers 148 can also act as sets of one or more switches or be otherwise realized to adjust and control the operation of the sensing module 56 in order to provide sensing at one or more sensors. The stimulation module also communicates with the wireless module 210 in order to provide power and/or data wirelessly to components of the system 8, such as an implantable neurostimulator or directly to human target tissue as may occur in TMS treatment for disorders such as depression, migraine or headache. One or more alerting components 156 may include a vibrating buzzer, speaker, light emitting diodes, etc. may be provided for notifying a user or patient about information relevant to therapy. This can include an indication, for example, that a treatment session is completed or is scheduled to occur, an impedance value is above a selected amount, a time has elapsed, the power has fallen below a selected amount, or other problem has occurred with the neurostimulator 51 a.

In an embodiment, at least one port 144 enables communication to occur by way of the communication module 68 between the device and other components of the neurostimulation system 10 such as a USB, micro USB, or conductive cable connects to an I/O interface 168 module that can have isolation electronics such as an isolator 158 and isolated DC-to-DC converter 160 in order to electrically isolate at least one of the I/O ports 144 a,144 b from the other circuitry and components of the neurostimulation system 8. The neurostimulator 51 a can also include a power management/charging module 74 with a power management circuitry to regulate power operations. The power management/charging module 74 can include, and be disposed between, a battery 142 and the processor 58. The power management module 74 can have components to charge the battery 142, such as a wireless power harvester (e.g. induction coil configured for receiving energy by magnetic induction or rectennae configured for receiving RF or microwave energy) and associated circuitry, and/or can be configured for recharging the battery 142, using power from an I/O port 144 b. One or more fuses can provide for both patient and device safety, such as fuse 164 disposed between the battery 142 and processor 58, or battery 142 and the other components of the power management/charging module 74. Regulators can be provided such as regulator 166 for maintaining a constant supply voltage to the I/O interface 168 when I/O ports 144 a and/or 144 b are connected to external equipment. Although shown as portable devices, the neurostimulators shown herein may be configured to be recharged using power converter that is plugged into a wall socket, with appropriate safety.

FIG. 10A, shows a menu screen of a computer system such as a computer in a medical clinic that is connected to the internet. In an embodiment related to use of neurostimulators 51 a in a clinic, the computer may serve as a user/physician programmer 70. The menu screen 170 is a user interface and includes virtual buttons that allow selection of operations related to managing one or more neurostimulators 51 a. Each virtual button of the menu screen 170 can be supported by a corresponding module which includes all software and hardware required for implementing related tasks. For example, the manage treatment credits button 172 a is part of a module that allows for purchasing treatment credits to be used with a particular neurostimulator 51 a, and can operate with the payments and permissions module 202 of the system.

The user of the menu screen 170 may be a patient, doctor, technician, health care professional, office employee (with sufficient permissions), or anyone that manages treatment sessions with patients. The menu screen serves as a user interface that allows for user input and may be configured differently for different users. Pop-up dialogue boxes with fields for user ID and passwords can be presented to a user for making certain selections or adjustments. Clinics staff can enter ID codes assigned to the clinic in order to modify, view, and selectively adjust values related to a patient account, including managing payment credits, patient customer's account and related to programming and/or setting operating parameters of a neurostimulator 51 a. The menu screen 170 is accessible from web-based application using a physician programmer 70 or computer.

A screen component shows status settings 174 related to one or more devices being adjusted by a user operating the menu, including device identification and use/connection status.

A button control, and associated module, is shown for managing treatment credits 172 a. This selection invokes additional screens for managing and purchasing treatment credits, requesting treatment credit refunds, and for viewing a history of treatment credit transactions. It can also include dates and times of treatment credit purchase, download, therapy provision, patient ID and reimbursement code information, and other information. In an embodiment, a treatment credit can contain data fields having information about characteristics of the therapy to be provided such as the maximum treatment session duration, or can contain an interval or date during which the stimulation may be provided. Treatment credits may be provided with an expiration date after which they can no longer be used and become “expired”. These may be exchanged for new treatment credits or “refreshed” using the module.

A button control, and associated module, is shown for refreshing/restoring 172 b which will update the values on the status screen 174 to reflect for example, the current number of treatment credits for one or more neurostimulators 51 a. The selection can also provide screens with options to, for example, restore a device to its default values, clear device memory, etc.

Additional selections that are provided include a button control, and associated modules, for adjusting account information related to a clinic or patient 172 c.

Additional selections that are provided include a button control, and associated modules, for providing technical support such as viewing manuals or instructions on how to operate the device, or providing a chat window with a customer service representative 172 d.

An additional selection that is provided is a button control, and associated module, for performing a calibration or diagnostic routine and displaying the results including whether the device passed various tests 172 e. The selection can allow for running diagnostics such as a diagnostic check on a device 51 b using a USB or other cable (loop-back cable), or by sending instructions and receiving data related to calibration and system test results wirelessly and if necessary requesting technical support 172 d.

An additional selection that is provided is a button control, and associated module, for managing or requesting reimbursement for treatment by a patient's insurance company 172 f.

An additional selection that is provided is a button control, and associated module, for viewing usage and compliance 172 g. This permits obtaining, viewing, and managing historical data records related to usage, and further presented in relation to compliance criteria. Menu screens invoked when this button is selected can provide for a graphical or table view of the usage of one or more neurostimulators 51 b. This can include information on patient ID, number and ID of associated treatment credits and reimbursement codes and payment information associated with the credits. This can include screens of patient usage as shown in FIGS. 7a and 7b . This can also include screens that allow for programming of compliance criteria such as weekly treatment goals as well as what to do in the case that criteria are met or fail to be met. Options related to how, when, and what information is queried of the patient (e.g., about symptoms, medication compliance), and scheduling presentation of survey items is also provided.

A button control, and associated module, is shown for allowing a user to adjust or run a treatment session 172 h using an invoked menu interface to select or adjust a stimulation program and control the neurostimulator 51 a to provide treatment. The treatment module 172 h and control module of the neurostimulator may both contain non-transitory machine-readable storage media configured to store machine-executable instructions that is executed by processors of the system and can also include, for example, a look-up table, formulas, algorithms, a database having a matrix of treatment protocols and values associated with the protocols. For example, each column associated with a particular treatment contains parameter value settings such as frequency, amplitude, duration, duration of therapy, stimulator at which the signal is applied, inter-therapy intervals during which stimulation is not provided, number of maximum treatments allowed per day, number of total time allowed per day, maximum stimulation strength allowed, and any other operational parameter related to treatment with neurostimulator that is external or implanted.

An additional selection is an “Administrative” button control 172 i, and associated module, for providing administrative operations which invokes additional screens that allow for changing passwords and/or user IDs, for defining allowed ranges for stimulation parameters, for registering a neurostimulator to a particular patient (which can include options for viewing and modifying device information of the neurostimulator 51 a).

An additional selection is a “Login/logout” button control 172 j, and associated module, for allowing the device 51 b, user/physician programmer 70, or remote user/physician programmer 70′, to establish and terminate communication with each other or with the Management Computer 71.

FIG. 10B, shows an embodiment of a menu screen of a computer system device of the system 10, which can be used for setting usage and compliance parameters. Usage parameter values 176 can be set for maximum and minimum amplitudes used during stimulation as well as the number of leads at which stimulation is provided (which may be allowed per treatment credit) and the frequency at which stimulation occurs. Additionally parameters may include inter-stimulation pauses during which stimulation is not provided, ramping up or ramping down intervals which allow for smoother therapy onset and offset in order to deter disturbing a sleeping subject, maximum duration or # stimulations allowed for a given interval “dose”, and any of the other stimulation parameter settings or limitations disclosed herein. Settings related to compliance 178 can be adjusted including, for example, number of days per week that stimulation should occur during the day (and the minimum and maximum time for each session). In this example, since the maximum amount of time is 2 hours the device may be set to not allow stimulation to occur longer than 2 hours in any particular 24 hour period if a “number of sessions per day” is set to 1. Compliance can also be set for the number of nights per week that stimulation should occur (and the minimum and maximum time for each session—in this example there is no maximum time limit). Compliance restrictions may also be related to dose-based criteria, for example, a higher amplitude stimulation signal can be associated with a shorter allowable interval (or total duration “on” over a selected interval) so that the “dose” remains approximately similar. Dose-based compliance relationships can be linear, such as doubling the stimulation amplitude (or number of pulses provided by a TMS coil) which can result in a halving of the maximum allowable duration or number of stimulation sessions allowed per unit time. Alternatively, strength/duration dose relationships may be non-linear and non-proportional. For example, in the treatment of depression, if the neurostimulator includes a TMS coil that delivers “N” pulses of “S” strength, and the user increases the number of pulses to 3N, then S may be reduced to 90%. The strength/duration, strength/number of treatments per unit time, or strength/number of stimulators used to provide stimulation, relationships defined by compliance criteria or other restrictions related to the provision of stimulation (e.g., defined in the payments and permissions module) may be defined in various manners. It may be defined by a prescription of a patient that is written by a doctor and realized in electronic form by the system, by findings of a safety study, by the severity of a disorder, by patient response to therapy, according to answers of survey questions, according to improvement seen during therapy, by drugs taken concurrently as part of treatment, by the patient's measured tolerance for pain, or otherwise and may be stored in a look-up table or defined by an equation of the set compliance module 178 which works with the compliance module 200 and other modules of the system.

The treatment session credit field shows that there are 60 treatment credits remaining prior to the device no longer allowing the user to provide stimulation sessions. Also a selection has been made to configure the system to cause a decrement of one treatment credit each day that the user provides at least one stimulation session. If “session” had been selected then each time the user provided a stimulation session lasting longer than a selected amount (e.g. 5-30 minutes) then the treatment credit value would be decremented by 1. If the user stops before a minimum time limit (e.g., 5 minutes), then the session may not count and the treatment credit is not adjusted. An activation interval is also shown and the value is 90 days. This indicates that the neurostimulator will remain activated for 90 days from the current date. The treatment credit or activation interval fields may contain values or be left blank. If an interval of activation limitation is used without a treatment credit limitation, then the device will continue to provide stimulation treatment until the end of the interval. In an embodiment, in the case where no maximum is defined for the day/night stimulation fields (e.g. currently set at 3 and 3, where “3+” would signify “at least 3”) then the user would be allowed to use the stimulator as many days as desired before the expiration date defined by the 90 day interval. There may also be compliance rules set up combination rules that utilize “if”, “and”, and “not” logic, such as a rule which does not allow stimulation to occur during the day if stimulation was provided the preceding night. In embodiments, the system 10 or neurostimulator 51 may be required to check (either periodically or before each use) for an active prescription (in a wired or wireless manner) in order to ensure that a doctor intends stimulation to be available. Like the treatment credit information, the prescription data stored in a computer 71,70′ can also set limits for the maximum number, or length, of stimulation sessions per day. The current settings can be compared to the prescription if the “check prescription” value is set to “Y”, which sets an operational flag in the payments and permissions module 202.

An “Alerting” button control 172 k, and associated module, allows for setting alerting parameter for system components including device 51 b, user/physician programmer 70, remote user/physician programmer 70, can also be used to alert a patient's smartphone, a customized EXD-pager type device worn by the patient, or remote Management Computer at a remote site 71 to send an alert (e.g., via e-mail or text message) to a patient to alert to various events including an upcoming therapy session, or to remind a patient if the therapy session was missed.

A “Non-Compliance” button control 172 l, and associated module, allows setting parameter values and operations that contingently occur due to various types and thresholds of non-compliance. For example, alerting may also be set up to send an alert from the user programmer 70 to a clinic's computer 70′ if the patient is severely non-compliant and device usage data meets a non-compliance threshold criterion established for the compliance module 200, for example, the data shows a failure to provide any therapy over the span of a month.

Another selection that is provided is a “QOL/Diary” button control 172 m, and associated module, for allowing setting of operations related to obtaining quality of life (QOL) data and/or bladder diary data. For example, survey items for an electronic bladder diary may be presented to a patient on a defined schedule such as once a week. The data may be processed in different manners such as being used to generate summary statistics and trend graphs related to symptom improvement over time. The QOL/Diary/symptom data may be transmitted with other data to a computer in a clinic 70′ so that this can be reviewed by a doctor prior to, during, or after a patient's clinic visit. The bladder diary items may be presented to a user visually in textual format with graphics where appropriate, or can be presented through a speaker of a device using text-to-voice technology or using pre-recorded messages. User response can be obtained by a user interacting with the neurostimulator or patient programmer 70 to select a score (e.g. choosing between 1 and 7, on a 7 point likert scale), or by voice, if the device is configured with voice-to-text recognition. A user's responses can simply be digitally recorded and analyzed at a later time by a transcriber service. The non-compliance criterion can also be defined for the provision of QOL, bladder diary, or other survey responses data. User response data can occur across 1 or more scheduled sessions. Although QOL and bladder diary information are used in this example, the neurostimulator 51 a can be configured to provide any type of assessment instrument or survey items related to a disorder suffered by, or condition to be modified in, a patient. This may include the assessment of depression, migraine, memory, pain, sleep apnea, anxiety, hypertension, tremor, concentration/attention/focus, reaction time, etc.

A “Send to Device” button control 172 n, and associated module, allows the user to update the neurostimulator 51 a and/or the programmer 70 with the new settings.

A “Send to Memory stick” button control 172 o, and associated module, allows the system to enable the updating of the neurostimulator 51 a by providing the information on a memory stick that is given to the patient. When a patient does not want to visit a doctor's clinic and does not have access to internet or cellular coverage, or who may not be comfortable operating a computer, a memory stick may be provided which can simply be plugged into an I/O port 114 of a device 51 a. This will provide an update to the device data and allow for continued treatment of a patient. Routines a communication module 68 can allow upload of all device information (including usage and compliance) to the memory stick. This can then be sent back to the doctor's office so device data can be reviewed.

A “Generate Code/Tones” button control 172 o, and associated module, allow for a code to be generated which can be printed out and sent (mailed/e-mailed) to a patient who can then enter the code into the neurostimulator 51 a or programmer 70 using the user interface module 76 in order to allow for continued treatment of the patient. The code may extend the duration during which the device may be used, or increase the number of treatment credits which are present in the device. In embodiments, instead of a code, a barcode or the like (Data Matrix and QR Codes) can be printed out and the programmer 70 can read the code via a digital camera in order to re-activate the device. In embodiments, a computer can use a sonic protocol as is done by facsimile machines co communicate with a device 51 a over a phone line, with appropriate modulation, handshaking, and demodulation implemented within the transmission protocol.

In an embodiment, operation of the menu screens shown in FIGS. 10A and 10B displayed to a user by a computer system, allows patient selections that cause a first processor of the control module 52 of the user/physician computer 70 to transmit data signals to a second processor of a remote computer 70′ (or 71) which has been configured with communication 68 and control 52 modules designed to receive and operate upon the information data sent from the first processor. Further, the second processor is configured to access information values stored in memory 60 such as in at least one table that can be related to treatment of a patient such as: parameter values for a stimulation program, treatment credits, activation interval during which the device 51 a is permitted to operate, values related to a status or limitations of a prescription of a patient, compliance data and/or criteria of a patient, payment information of a patient, insurance information of a patient, payment and identification information of a clinic, rights and privilege information that is related to a user of a neurostimulator, maintenance information related to a neurostimulator, and/or geographic location information related to a neurostimulator if the neurostimulator (or other system component) has GPS or uses other geo-location technology.

The information can be operated upon by the processor of the remote computer according to algorithms and rules related to compliance, payment, and provision of stimulation therapy by at least one neurostimulator 51 a. The second computer can then transmit the result data of this processing as result information data to the physician computer 70 in order to select, update, adjust, allow, disallow, or otherwise operate upon the settings that effect operations of a neurostimulator 51 a in a manner that adjusts the provision of therapy for at least one patient. As is the case for the patient programmer 70 and other components of the subject invention, the components shown in FIGS. 10A and 10B can be used for stimulation systems which incorporate TENS and percutaneous stimulators as well as those having fully or partially implantable stimulators, and systems using implantable stimulators powered by external components. Combination systems can also be supported, such as providing TENS from an externally worn controller which also provides power to an implanted neurostimulator.

During a communication session when the neurostimulator 51 a communicates with the computer 70, a processor can cause information to be updated and stored in the memory of the neurostimulator 51 a. This can occur contingently based on user input operating the menu the menu screen 170. For example, if one or more treatment credits are purchased, or are otherwise renewed (e.g., based upon the user meeting compliance criteria), then the treatment credits are sent by the computer 70 and received by the neurostimulator 51 a processor and the number of available treatment credits is updated in the payment and permission module 202 in order to enable treatment sessions to occur. When the neurostimulator 51 a is in communication with the computer 70 or a computer system network that communicates, in a wired or wireless manner, with the computer 70 then parameter values used by the neurostimulator 51 a during operation (e.g. a permitted range of values for various parameter settings) can be adjusted.

TENS System and Method Embodiments

Although the SAFN or PTN may be stimulated using generic TENS stimulators having at least a first and second TENS electrode that can be placed to provide stimulation of these nerves, recent TENS technology has moved towards specialized systems which are wireless and which use pads or electrode arrays and also provide features which promote better treatment response and easier patient experience. FIG. 11A shows an embodiment of a system for providing SAFN TENS stimulation of a patient 6 which includes at least two adhesive TENS pad electrodes 30 e, 30 f that are disposed within a leg applicator accessory 220 which may be a garment configured for positioning at least one electrode on the medial upper calf area. The garment maybe a customized sock, wrap, or similar type of shaped garment that can be worn by a user. In this embodiment leg applicator accessory 220 serves to position at least two TENS stimulators within the material and along the medial leg surface with the first positioned approximately several inches below the knee and the second located about midway between the first electrode and the medial malleolus. Although the accessory 220 is shown here forming a sock, the accessory 220 can be designed extend distally only to a location cephalad to the medial malleolus and does not need to cover the foot. A lead set 86 c can travel within the garment or be routed along he garment and communicates the stimulation signals to the electrodes 30 e, 30 f from a neurostimulator 50 (not shown), which may be strapped to a patient's leg, worn around the patient's waist, or disposed in a pocket on the top of the accessory 220. The electrodes can operate in a bipolar manner with electrodes 30 e, 30 f or these can both be referenced to an additional electrode, which may be on the bottom side of the neurostimulator. Rather than both electrodes being below the knee, one can be above and the other below as may occur with a knee sleeve electrotherapy garment with dual electrodes. Typically, when a conductive fabric is used, this should be formed within the conductive garment areas isolated so that stimulation can be applied to the SAFN without stimulating other targets such as calf muscle or the sural nerve on the lateral side of the leg. A shaped area of electro-conductive garment 31 is shown around electrode 30 f.

FIG. 11B shows an alternative embodiment of a system for providing SAFN TENS stimulation of a patient 6 which includes at least two adhesive TENS pad electrodes 30 g,h and 30 i,j (j is not shown) that are disposed within each of two upper leg applicator accessories 222 a, 222 b, made of a formed and/or elastic garment material that can be worn by a patient and which serves to position the stimulators along the medial leg surface approximately at or below the knee to 3 or 4 inches below the knee (although in embodiments it may extend to just above the medial malleolus). The stimulation provided by the embodiment in 11B may be suitable for stimulating the infrapatellar branch of the SAFN, which may be less comfortable for some users and may also be more difficult to assess with respect to confirming correct placement of the electrodes. A lead set 86 d communicates the stimulation signals from a neurostimulator 51 c which here is shown disposed on the top of the accessory 222 a (it can be configured to be snapped onto the garment or held in pocket disposed in the garment), to the electrodes 30 g, 30 h. An electrode pad 30 i is shown on accessory 222 b which communicates to another neurostimulator (not shown), in order to provide bilateral stimulation. Alternatively, all electrode pads can be connected to a single neurostimulator using a wire that runs up one leg and down the other. When two neurostimulators are used, they may communicate in a wired or wireless manner in order to synchronize the stimulation of both legs so that the signals applied to the first and second leg occur at a desired lag, which may be a delay of zero as set by the stimulation protocol. When a 10 Hz stimulation signal is applied to each leg 180-degrees out-of-phase, then the stimulation may project caudally at 20 Hz at locations commonly innervated by the peripheral signals from each leg.

FIG. 11C shows an alternative embodiment of a system for providing SAFN TENS stimulation of a patient 6 which may be more simple because it does not have free-standing lead wires. The neurostimulator 51 d can be realized in a basic embodiment that has only a few controls and no wires. The neurostimulator 51 d has a first wing 224 a having a top side with a first control 16 a which is a plus symbol “+” and a second wing 224 b having a top surface with a second control 16 b with a negative symbol “−”. The neurostimulator 51 d components are contained within a housing having a center region with a battery compartment 228 for accepting at least one rechargeable or disposable battery 142 which powers the neurostimulator 51 d. The control module 52 of the neurostimulator 51 d is connected to the first and second user interface controls 16 a, 16 b. The user can turn on the device 51 d, under control of the control module 52 by pressing the user interface controls according to defined patterns. For example, pressing the first and second button 16 a, 16 b for 3 seconds can turn the unit on and doing this again will turn it off. The user can increase the stimulation by pressing the first control 16 a or decrease the stimulation by pressing the second control 16 b. In an embodiment, after the device is turned on and connected to a user to obtain sufficient impedance levels, it will provide a timed stimulation session which lasts a selected interval such as 30 minutes, after which the device may power down. Alternatively, the device may continue periodically (every 2 hours) provide additional stimulation sessions (e.g., pulse rate 5 to 50 Hz and pulse width 150 μs) as long as it remains connected to a user. The first and second wings are made of a flexible material such as rubber or silicon and have snap connectors 89 a, 89 b on their bottom surfaces (that receive stimulation signals by a lead set 86 e that resides within each of the first and second wings) which attach to an electrode array comprising two electrodes provided as a reusable adhesive electrode pad that has the same shape as the device 51 d and which snaps onto the connectors 89 a, 89 b of the first and second wings. Signal transducers for providing alert signaling 156 can include a led diode or speaker provided on the top surface of the first wing in order to notify the user about the start or stop of stimulation therapy and also can provide a warning alert if either electrode pad is not attached correctly as can be measured by an impedance module or other electronics that can detect this problem. The unite can use codes such as “a single long high beep” or “two long high beeps” where high is 1000 Hz or a low buzz (500 Hz) if, for example, the power management 74 indicates that the battery 142 is low. Voice messages can also be used. A communication module may also be provided to enable the stimulator 51 d to wirelessly send and receive data and be controlled by a smartphone which can serve as a user/physician programmer 70. Additionally, diodes or an LCD can allow signaling of information such as battery charge.

In order to maintain the neurostimulator 51 d in position at least a first strap 229 a is provided which is attached to the first wing 224 a and configured to wrap around the calf area to secure the first wing the user's leg. Additionally, a second strap 229 b may be provided which is attached to the second wing 224 b and configured to wrap around the calf area to secure the second wing to the user's leg. The straps act to secure the neurostimulator 51 d in position and bias each of the wings and the TENS attached to the bottom surface of each wing against the user's leg. A strap can also be configured to be attached to the housing of a neurostimulator or an electrode array rather than the two wings. The strap is configured with a length and fastening means which allows for the strap to wrap around a leg circumference of between 30 to 48 cm corresponding to that expected in the calf area of an adult user (McDowell et al Anthropometric Reference Data for Children and Adults: United States, 2003-2006).

When the neurostimulator 51 d is configured to work jointly with an implantable neurostimulator which is controlled by an external controller, then conduits 86 a may conduct energy to power either RF or magnetic transmitters in order to power the implanted device. Alternatively, the RF or magnetic transmitters can be located in the housing of the neurostimulator 51 d and the neurostimulator 51 d may be configured to also provide TENS either concurrently or at a different time than the implantable neurostimulator provides stimulation. The neurostimulator 51 d can be controlled by a user programmer 70, which may also control the implantable neurostimulator either by communicating directly or by working jointly with the neurostimulator 51 d.

FIG. 12 shows an embodiment of a method for performing OAB treatment such as an SAFN stimulation treatment session using a neurostimulator 51 a. Various steps may be performed in a different order, omitted, or repeated. In a general embodiment the steps of FIG. 12 can occur so that the device is operated based upon a verification-treatment basis. This means that when one or more defined verification criteria are met, stimulation treatment can be provided to a patient. The verification step can simply entail assessing if a per-treatment session payment credit is available, and if not then a payment must be made before the neurostimulator 51 a is “verified”. For example, during verification the number of stimulation-credits of the system 10 is assessed and must be above a selected value for verification to be true. Once verified the device is granted permission (i.e., set a verification status flag to true) to provide stimulation. The stimulation treatment credit value is decremented by a value of 1 either in a device 51 a or in a user/programmer 70 before, during, or after the stimulation is provided. The permission flag may have a time limit such as a subsequent interval of one hour, 2 hours, one week, or other defined interval. The decrement in treatment credit value may only occur after a stimulator 51 a has been used for a minimum amount of time such as 7 minutes in order to avoid charging a user for an “incomplete” stimulation session that does not last a minimum duration. In step 230, a user (patient or physician) obtains a neurostimulator 51 a and performs the additional steps to set it up.

In step 232, a user establishes a user account on the computer system. If the neurostimulator 51 a has not been previously used by the user then the user can link the neurostimulator 51 a with a user account and/or user ID. The user ID may be for a clinic when the device is used in a clinic or may be for a patient who will be treated by the clinic. The User ID can be for a user when the device will be used at a patient's home. Preferably, the payment and permission module 202 of a neurostimulator has, or is assigned, a unique identification number by which it is identified during communication/transaction with a computer system.

In step 234, a user can sign into a user account, navigate to a menu 170 and select, for example, a choice of “manage treatment credits” 172 a that enables the purchase of one or more treatment credits. Each purchased treatment credit that is uploaded to the physician programmer 70, and/or the neurostimulator 51 a preferably includes data and a unique identification number.

In step 236, communication between a neurostimulator 51 a and a computer system (which may include any of 70, 70′, 71 and communication therebetween) is established using wired or wireless communication. Communication can also occur between the computer and a memory stick which will then be used to transfer data and credits to the neurostimulator during a separate step. The modules can be stored and operated on a server computer having a processor and control module configured to provide user accounts that can also allow management of user and device information. The communication can include reading and/or adjustment of initial parameter values that are set for the device 51 a at the start of the communication session and final parameter values that exist at the end of the communication. Step 236 can include a step of providing information to a user on a display 174 of the physician programmer or on a display 79 of the neurostimulator 51 a.

After verification that the neurostimulator 51 a is an authorized device 238 that has been associated or “linked” with a particular user account and/or user ID, in step 240 the computer system transmits one or more treatment credits that are available or which may be purchased to the neurostimulator 51 a. Alternatively, as has been disclosed, information could be transferred between the computer system and the neurostimulator 51 a using a digital storage device such as a flash drive as part of step 240. In step 240 a code can be generated that is simply manually entered or optically scanned into the neurostimulator 51 b by a user and operation of the payments and permissions module 202 has been previously programmed to interpret the code to provide appropriate functionality.

Transmission of a purchased treatment credit between an external computing device and the neurostimulator 51 a, can include one-way or two-way communication of information related to number of remaining treatment credits available (if any), the total number of treatment sessions (and associated times and intervals) which have already been provided, or which are scheduled to be provided by the neurostimulator 51 a, a count, including details, related to “incomplete” treatment sessions that did not last longer than a minimum amount (and related details), information related to the use of a particular treatment credit based on a unique serial number and any associate information related to a user account, user ID, patient ID, and other operational information. Instead of treatment credits and especially in the case where a user of the neurostimulator is used by a patient rather than a physician, if the device is “verified” due to patient data and/or payment information meeting all relevant criteria (i.e., a patient has met all defined compliance criteria and the patient is paid up through the current month, etc) then the device may simply be verified and information is sent which allows the neurostimulator 51 a to operate for an upcoming period such as another month, after which the user must “renew” the neurostimulator 51 a.

In step 242, the patient or administrator operates the neurostimulator 51 a to provide a treatment session. In step 244, the neurostimulator 51 a determines whether the device is “verified” which may simply entail determining if a treatment credit is available. However, even if a treatment credit is available, if the patient has not met compliance criteria or if a prescription for the patient using the device has expired then the device 51 a may not provide stimulation. If the device is verified then the neurostimulator may provide treatment and perform contingent operations such as managing a parameter value associated with treatment credits. If it is determined in step 244 that there are no more available treatment credits or that the device is not “verified”, then the user must return to step 240 to purchase additional treatment credits before another treatment session may be performed or the device may be otherwise verified.

If a treatment credit is available, and the device is verified then the nerve stimulation 51 a performs a treatment session using one of the treatment credits purchased and transferred to the neurostimulator 240. In performing the treatment session, the neurostimulator 51 a activates the pulse generator so that current pulses of a stimulation signal traverse the stimulation site during the treatment session by passing between stimulators such as from the TENS electrode 88 to the percutaneous electrode needle 28. If the device is operated on a pay-per-session basis then after a treatment session is performed, the number of available treatment credits is reduced by one. Step 242 is then repeated when another treatment session is desired. In embodiments, the system allows for devices to be verified although a treatment credit value may be negative reflecting a treatment credit deficit.

Methods for providing therapy are shown in FIG. 13A, where in a first step 250, a needle electrode is percutaneously inserted in the leg at or below the knee at a position known, or determined to be, appropriate for stimulation of the SAFN.

In a second step 252, an assessment procedure is performed wherein the signal provided by a neurostimulator 51 b is increased in steps (e.g., 0.5 uA) from a starting value to a value at which the patient experiences tingling, warmth, pressure, vibration or other similar sensory event which has been determined to indicate that the SAFN is stimulated. Typically this should include a sensation that radiates away from the site of the electrodes and often will spread down the leg and even towards the hallux (or up the leg if a stimulator is located near the foot). The stimulation level is then increased from above nerve recruitment threshold to a level that is greater but not painful to the subject and is provided during treatment. If the patient is not able to feel “tingling”, or if it occurs at an amplitude that is higher than what is expected for that patient (compared to previous sessions of that patient) then the needle electrode may be re-oriented or inserted in a new location, and the assessment is done again. The stimulation is then typically halted while the assessment is done for the PTN stimulation site. An assessment mode of the device may provide an assessment signal which increases its amplitude or pulse width in order to allow the patient to better confirm the spreading sensation.

In some embodiments for combined SAFN and PTN stimulation, a step 254 may be done in which a needle electrode is percutaneously inserted in the foot or leg at a position known, or determined to be, appropriate for stimulation of the PTN.

In step 256, the signal provided by the second neurostimulator 51 a (or a second stimulus generator of neurostimulator 51 b) is increased in steps of 0.5 uA from a starting value to a value at which the patient experiences a foot twitch which indicates that the PTN is stimulated. That level is the used to adjust the stimulation amplitude that is provided during treatment. If no foot twitch is seen or measured from a sensor, or if the subjective sensation of a muscle response occurs at an amplitude that is higher than what is expected for that patient then the needle electrode is removed, inserted in a new location, and the assessment is done again. The stimulation is then typically halted for the PTN stimulator.

In the fifth step 258, combination stimulation is provided to both the SAFN and the PTN according to a selected therapy protocol whereby the signals for the first and second stimulators are provided and therapy continues for the selected therapy interval such as 30 minutes. For example, the stimulation may alternate between the SAFN and the PTN, may occur simultaneously, or may occur as otherwise designed. A variant of this method can include using two stimulation sites which are both SAFN. Sites can be selected on the same or different leg. Although this method is oriented for percutaneous stimulation, a similar method can be used for combination TENS therapy where the stimulation of the SAFN and PTN are assessed separately before stimulation therapy is provided.

As shown in FIG. 13B, in a first step 260, at least a first TENS electrode is attached to a subject's leg at a position known, or determined to be, appropriate for stimulation of the SAFN, while at least a second TENS electrode is placed nearby, preferably lower on the medial surface of the leg or at a location such as the inner sole of the foot.

The TENS approach to electrically stimulating the SAFN for the treatment of OAB will typically involve placing at least one pair of surface electrodes placed on the medial aspect of the lower leg (e.g. step 260 of FIG. 13B), with one electrode slightly below the knee. Placement of the electrodes may target the SAFN branches that travel subcutaneously from the level of the knee down to the ankle but electrodes on the medial aspect of the sole of the foot may also be found to provide effective bladder modulation. Anatomical studies in human cadavers report a high degree of variability in the anatomical location of the SAFN branches (Wilmot, V. V. and Evans, D. J. R. (2013), Categorizing the distribution of the saphenous nerve in relation to the great saphenous vein. Clin. Anat., 26: 531-536). As such, the optimal electrode configuration may vary from one patient to another. In general, the SAFN emerges as either single or multiple fascicles at the level of the knee, immediately posterior to the medial condyle of the tibia. These travel along the medial aspect of the leg and can be located either anterior or posterior to the saphenous vein. Anatomically, the saphenous vein is located along the posterior margin of the tibial bone. Therefore, the main SAFN may be located more anterior or posterior to the posterior margin of the tibia. Placing the electrode too posterior to the tibia may result in the electrode being directly over the medical gastrocnemius muscle, which may be electrically activated during stimulation. This unintended muscle activation may cause discomfort to the patient. If this occurs, the electrode should likely be repositioned and stimulation tried again to avoid this.

In a second step 262, an assessment procedure is performed wherein the signal provided by a neurostimulator 51 b is increased in steps (e.g. 0.5 uA) from a starting value to a value at which the patient experiences a tingling sensation radiating along the leg which indicates that the SAFN is being modulated. That level can then be used to adjust the stimulation amplitude that is provided during treatment 266. If the patient is not able to feel the expected sensation, or if it occurs at an amplitude that is higher than what is expected for that patient (compared to previous sessions of that patient) then at least the first TENS electrode is removed, applied to a new location on the medial aspect of the leg, and the assessment is done again. Rather than moving a single electrode, an electrode array or neurostimulator having pairs of electrodes can be moved.

During assessment of the SAFN 262, a doctor or patient may be instructed that correct electrode placement and electrical stimulation of the SAFN may be determined if a patient can confirm a “tingling” sensation that radiates below the site of stimulation. If stimulation evokes a foot motor response, then the selected electrode placement and/or selected stimulation signal may be (co-)activating the tibial nerve. In this case, it may be beneficial to change the location of one or more electrodes and re-assess.

With respect to adjusting stimulation characteristics 266, amplitude is typically set at the maximum value that is tolerated by the patient in the case of PTNS treatment. This may also occur in SAFN therapy, or the SAFN stimulation protocol may be distinct. For example, the protocol may instruct a user to determine the maximum stimulation and then reduce the amplitude by 10%, 20% or 50%, as long as nerve activation still occurs. In order to ensure that TENS is effective, it is likely that the minimum amplitude used for treatment will be defined by the amplitude at which the proximal electrode (e.g., location 29 b) evokes a sensory percept that spreads away from the electrode down the leg. This indicates that the subcutaneously located SAFN fascicle(s) are activated by the proximal TENS electrode.

In an embodiment, at least one surface electrode will be placed within the upper one-third of the lower leg to target the main fascicle(s) of the SAFN. The return electrode may be placed at more distal locations, such as the mid-point between the knee and the foot (29 d or anterior to this location), 5 cm cephalad to the medial malleolus (29 c), or the medial aspect of the sole of the foot (location 88). When stimulation characteristics of the signal are adjusted 266, polarity can be assigned as part of the stimulation protocol. The polarity of each electrode may be set to positive (anode) or negative (cathode), or this may be adjusted depending on the preference indicated by the patient based upon subjective comfort, or this may change during the stimulation.

In the fifth step 268, stimulation is provided to at least the SAFN of one leg according to a selected stimulation protocol for the selected therapy interval such as 30 minutes. The method can also perform the assessment or treatment bilaterally or choosing the leg that shows stronger recruitment.

FIG. 14 shows a system 8 a for providing TENS stimulation including an electrode array 270 having three TENS electrodes 30 j,k,l which are connected by conduits 85 a,b,c to three connector sockets 272 a which reside within a receptor base 274. Rather than connector sockets a connector can contain routing circuitry and other electronics which can be under control of the neurostimulator 50 a or the programmer 70. A first strap 276 can be configured as first 276 a strap portion and second 276 b strap portion which are connected to the array 270 on their proximal ends and which have fastening portions on their distal ends (e.g. Velcro) or which may be made of a sports wrap type material that allows the strap portions to grip each other without sticking to the leg of the user 6. A second strap 278 may also be provided on the bottom end of the array 270. Rather than being connected permanently to the array 270 the straps can be configured to snap onto the array. The receptor base can be formed of plastic or rubber and is shaped to receive a neurostimulator 50 a which snaps into the connector sockets 272 a to reversibly attach the neurostimulator 50 a to the electrode array 270. The array can be formed of a foam, silicone, or rubber material which is flexible and which provides for routing of the conduits 85 to the TENS electrode pads 30. The view shown is the top side of the array 270 and the bottom side is disposed with 3 areas of electrode hydrogel or conductive material provided on the TENS electrodes for connecting to the user's skin. There is also provided a user/physician programmer which may be realized as a smartphone on which a software application has been downloaded or by a customized user interface device (a battery powered remote control) which communicates with the neurostimulator 50 a or electronics provided on the array 270 in a wired or wireless manner. When provided as a kit, the array 270, neurostimulator 50 a, programmer 70, and instructions for use 276 may be included. In an embodiment, the array 270 is designed to be disposable and provide for approximately 1 month of use.

In an embodiment, the stimulation protocol can stimulate by referencing the first TENS electrode 30J to the second and third electrodes 30 k,l if the patient can tolerate this. Alternatively, combinations of stimulation circuits which include electrodes 1 and 2, 2 and 3, 1 and 3, or 1 referenced to 2 and 3 (or 2 referenced to 1 and 3) can be selected based upon patient comfort or the success of different electrode combinations to recruit the SAFN and produce a tingling sensation that radiates down a subjects leg from the upper-calf where the array is positioned during use. Allowing a user to selectively and programmably activate unique pairs from the 3 electrodes based upon user input can allow a patient to select a stimulation montage that stimulates the SAFN well without having to physically remove and replace the array to obtain successful positioning of electrodes. It also may be that in some subjects increasing the size of the electrode field serves to recruit the nerve better, while for others only 2 electrodes work better. In an embodiment, only two TENS electrodes (or more than 3) are provided on the array. Electrode combinations can be determined during assessment 262.

FIG. 15 shows top (front) and bottom (rear) views of a neurostimulator 50 a on the top and bottom of the figure, respectively. The top side of the neurostimulator shows a display 79, a power button 14, a menu control 18, and dedicated buttons 16 which may be used for example, to increase or decrease stimulation amplitude. Interface port 114 allows for powering the device or for wired communication with other system components. The bottom view shows three connector sockets 272 b which connect to the corresponding sockets 272 a on the neurostimulator. Although the neurostimulator 51 b shown in FIG. 2 only has one connector on its bottom surface for connecting to a TENS electrode, the other 2 connectors can simply be inactive during percutaneous stimulation when that stimulator is designed to be used for providing therapy both percutaneously and transcutaneously.

In this system patients can begin OAB treatment by receiving percutaneous stimulation in a clinic for a number of sessions and then the neurostimulator can be used by the patient to provide TENS by interfacing with an electrode array. While the treatment credits can be used to manage in-clinic percutaneous stimulation, these can also allow for a month of TENS treatment per credit, when the neurostimulator is used at home by a single patient rather than in the clinic for many patients.

Kits and Methods for Providing TENS of the SAFN For OAB Treatment.

In an embodiment, the invention is realized as a kit having at least two TENS electrodes 88 configured to receive a stimulation signal from a TENS neurostimulator 50 a. The stimulation signal can be provided according to a stimulation protocol that is defined for stimulation of the SAFN for the treatment of overactive bladder. The kit also includes instructions 276 for using the neurostimulator for the treatment of overactive bladder disorder which includes instructing a user to applying at least one of the 2 stimulators on the medial aspect of the leg below the knee for the treatment of the SAPH nerve. In instructions 276 may alternatively include instructions to place at least one of the two TENS electrodes on the inner side of the leg in the area near the upper calf and then provide a stimulation signal in order to determine if at least one of a tingling, vibrating, buzzing, pressure, electrotactile tactile sensation, warmth, or tickling sensation is experienced as radiating away from the location of at least one of the two electrodes. Further, the instructions direct a user in the case where the sensation is not experienced, and the application of the stimulation signal fails to produce a radiating sensation indicating that the saphenous nerve has been stimulated, then performing the step of either increasing the stimulation signal or adjust the position of at least one of the two TENS electrodes. In the case where the sensation is experienced then provide a stimulation session using a stimulation strength that does not cause pain.

In one embodiment, determining if a sensation occurs includes determining if the sensation is radiating away from an electrode and down the leg towards or into the foot. Alternatively, instructions may also include directions to place a second lower electrode near the medial malleolus or the sole of the foot and determining if a sensation occurs includes determining if the sensation is either radiating away from the first electrode and down the leg, or away from the second lower electrode an up the leg.

The instruction 276 can include or be provided in paper or as part of the user interface module which has multimedia ability for providing instructions via the neurostimulator 10 a or the programmer 70.

In an embodiment, the at least two TENS electrodes can be realized as part of an accessory such as a garment or an electrode array that positions the electrodes on the medial aspect of a patient's leg with at least one electrode positioned 1-4 inches below the knee.

An external patient programmer can be configured to communicate with and provide user control of the neurostimulator and at least one of the neurostimulator and external patient programmer are configured to monitor usage and assess compliance with respect to a treatment program that is related to treatment of overactive bladder and to provide patient alert reminders related to a stimulation program that is defined for the treatment of overactive bladder.

In an embodiment, the stimulation signal is defined to be a pulse train modulated at 10 Hz, 20 Hz, or can be a signal that roves between 10 and 20 Hz. The stimulation signal may be defined to be at least one of: slightly above (e.g. 0.5 or 1 mA) skin threshold (Tskin) which is the level at which the stimulation is first felt and slightly below maximum tolerance (Tmax) which corresponds to the level at which a user experiences discomfort or pain. A signal may also be defined to rove between Tskin and Tmax, by continuously or periodically adjusting amplitude, stimulus pulse width, and/or period as may be defined for a sinusoidal waveform.

In an embodiment, a system component such as the neurostimulator or programmer determines the therapeutic protocol for a given week or longer periods using a pre-defined schedule stored in its memory. The schedule may be modified according to various factors such as time since the first therapy session, number of stimulation sessions provided since the start of therapy, rate of stimulation sessions provided since the start of therapy. Additional adjustment may be made based upon assessment of patient input data which indicates improvements, worsening, or no change in symptoms as calculated upon patient input data.

In embodiments, at least one system component operates at least one accelerometer and is configured to analyze the accelerometer data in order to determine if a user is active or ambulatory using at least one of activity data and orientation data. The accelerometer data maybe analyzed to determine if the patient is, for example, walking, getting out of bed, moving with a gait that is over a selected rate. In this case, a modification the system may modify operation such as pausing or decreasing the provision of stimulation until the accelerometer determines that the user has stopped being active.

In embodiments, the instructions may also incorporate methods and guidelines reviewed in other parts of this specification. Additionally, because percutaneous saphenous nerve stimulation at the level of the knee can be used to treat individuals with pain, the kit may be indicated for providing relief both pain and OAB. In this instance the instructions that are provided within the kit may instruct a user select the treatment mode related to the desired therapy and may also be instructed to position electrodes or an electrode array differentially.

In an embodiment, a method of treating an overactive bladder of a person suffering symptoms of the disorder includes the steps of applying TENS electrodes for stimulation 260 which can include establishing at least two transcutaneous electrical neural stimulation (TENS) electrodes 30 and establishing a neurostimulator 10 a configurable to provide a treatment stimulation signal to the TENS electrodes according to a stimulation protocol that is defined in, or selectable using, a stimulation module 54 for stimulation of the SAFN for the treatment of the patient's OAB symptoms. This also includes positioning at least one of the two TENS electrodes on the inner side of the patient's leg 6 in the area near the upper calf. An assessment procedure 262 can include the steps of actuating said neurostimulator 10 a to provide a test stimulation signal and assessment in order to determine if at least one of a tingling, vibrating, buzzing, pressure, electrotactile tactile sensation, warmth, or tickling sensation is experienced which radiates away from the location of at least one of the two electrodes. In the assessment 262 two steps may occur which include (1) when application of the test stimulation signal fails to produce a radiating sensation indicating that the saphenous nerve has been stimulated, then performing the step of either increasing the test stimulation signal or adjusting the position of at least one of the two TENS electrodes and (2) when the test stimulation signal produces the radiating sensation, then providing stimulation treatment 268 using a stimulation signal strength which is not painful to the patient. The strength can be iteratively assessed or adjusted during therapy in the case that the patient threshold for pain changes.

In the method, the step of determining if a sensation occurs may include the step of determining if the sensation is radiating away from an electrode and down the leg towards or into the foot. Alternatively, the application step may include the steps of providing instructions to place, or placing, a second lower electrode so that it is vertically displayed from the first electrode and near the medial malleolus or the sole of the foot and determining if a sensation occurs which can be either radiating away from the first electrode and down the leg, or away from the second lower electrode and up the leg.

The method may also include the step of providing user instructions, or instructing a user directly, and these can be related to actuating said neurostimulator to provide a test stimulation signal and perform assessment 262 and providing stimulation with various protocols 268. The user instructions can include at least one of: written instructions; illustrations of the leg with graphic depictions of the location on the medial surface of the leg where the TENS electrodes should be placed; illustrations of the leg with graphic depictions of the location on the medial surface of the leg where a TENS array should be placed; instructions provided by a mobile device app or a mobile device; an audio-message of instructions; verbal instructions; instructions to use a device such as an ultrasound, infrared, or electrical impedance device in order to located the saphenous nerve or saphenous vein; instructions provided in combination with either a virtual reality or holographic display; instructions provided by a mixed media technology such as a DVD, and, a website address where user instructions are provided.

In the method, at least two TENS electrodes can be realized as part of an accessory such as an electrode array 270 that positions the electrodes on the medial aspect of a patient's leg, or a garment 220. Additionally when the at least two TENS electrodes are realized within an electrode array 270 that is designed to be connected to at least one band 276 that is configured to be wrapped around the calf of a patient and to position the array vertically along the inner side of the leg and the first electrode is above the second electrode. The band may be configured to wrap around the area of a patient's upper calf to secure and bias the electrode to the calf. The band or garment 220 can be configured to be attached to at least one electrode and to wrap around the area of a patient's upper calf, mid-calf, or entire leg to secure and bias the one electrode to the area between the upper calf muscle and the tibia.

The method may further include providing or operating an external patient programmer 70 which is configured to communicate with and provide user control of the neurostimulator and at least one of the neurostimulator and external patient programmer are configured to monitor usage and assess compliance with respect to a treatment program that is related to treatment of overactive bladder and to provide patient alert reminders related to a stimulation program that is defined for the treatment of overactive bladder. Additionally, at least one of the neurostimulator and external patient programmer are configured with a user interface module 76 configured to query about bladder activity, bladder pressure, urinary leakage and/or urgency episodes measured by wearable or implantable sensors. In an embodiment, at least one of the neurostimulator and external patient programmer are configured to query the patient about a symptom characteristic such as severity or frequency related to overactive bladder symptoms and to store the response. Further, at least one of the neurostimulator and external patient programmer are configured to allow the patient to input information related to a bladder diary, including if a void event was associated with urgency or leakage. These may also be configured to query the patient to input information about whether any voiding events occurred during night, whether voiding events awoke the patient, or whether voiding events were accompanied by urgency or leakage.

The method can further include setting, instructing, or providing instructions related to setting a stimulation protocol that is defined for stimulation of the SAFN for the treatment of the patient's OAB which includes setting the stimulation signal to be at least one of: a signal between 5 and 20 Hz, a 10 Hz signal, a 20 Hz signal, and a signal that roves between 10 and 20 Hz. The stimulation signal can be defined in the stimulation module 54 to be at least one of: skin threshold (Tskin), maximum tolerance (Tmax), and a signal that roves between Tskin and Tmax, by continuously or periodically adjusting amplitude, stimulus pulse width, and/or period in the case of a sinusoidal waveform.

The method can also include an external patient programmer 70 that is further configured to graphically display data related to overactive-bladder-related symptoms as summary statistics or trend charts. The external device or programmer 70 can also determine the therapeutic protocol for a given week or longer periods using rules or lookup tables of the compliance module 200 based upon factors such as time since the start of therapy, number of stimulation sessions provided since the start of therapy, rate of stimulation sessions provided since the start of therapy, and improvements, worsening, or no change in symptoms as calculated upon patient input data.

The method can also include providing and operating an accelerometer for at least one system component and the system 10 a is configured to analyze the accelerometer data in order to determine if a user is active or ambulatory using at least one of activity data and orientation data. The accelerometer data maybe analyzed to determine if the patient is, for example, walking, getting out of bed, moving with a gait that is over a selected rate. In this case, the system may modify operation such as pausing or decreasing stimulation until the accelerometer determines that the user has stopped being active.

In an embodiment a system for transcutaneous electrical nerve stimulation in humans includes a housing 12 a stimulation module 54 having stimulation generator mounted within the housing for electrically stimulating nerves and an electrode array 270 releasably mounted to the housing and connectable to the stimulation generator, the electrode array comprising a plurality of at least two electrodes 30 for electrical stimulation of nerves. The user interface module 76 can provide at least one user control 16 mounted to the housing and electrically connected to a user interface module 76 working with the control module 52 to control the stimulation generator for controlling at least one characteristic of a stimulation signal generated by the stimulus generator. The sensing module 55 can provide monitoring circuitry mounted to the housing 12 and electrically connected to the stimulation means for monitoring impedance in order to assess electrode contact with patient skin 6. A user interface module 76 mounted within the housing 12 and electrically connected to the control module 52 for controlling the stimulus generator. A user display can be part of the interface module 76 and mounted to the housing and electrically connected to the control user interface module 76 and the monitoring circuitry of the sensing module 55 for displaying the status information related to the device 50 a. At least one strap 276 can be attached to at least one of the housing and the electrode array 270 and the strap is configured to hold at least one of the housing 12 and the electrode array 270 so that the array stimulates a specific anatomical location to treat OAB by stimulation of the SAFN using at least two vertically displayed electrodes 30. Preferably, the location is the medial surface of the upper calf area between the calf muscle and the tibia.

Co-Activation and Related Investigations of PTN and SAFN Stimulation.

The current invention is based upon the recent finding by the inventors, using both pre-clinical and clinical data, that the SAFN can be used as a target in the treatment of OAB and related disorders. Results of a recent study are shown in FIGS. 14 to 19. Co-activation of SAFN due to percutaneous stimulation of PTN was explored. This study was conducted, in part, due to the apparent differences in the stimulation amplitudes used to provide PTNS therapy in patients and those used in pre-clinical animal studies. In patients, PTNS is applied near the foot motor threshold (defined as “1 T”). Studies in anesthetized cats and rats show that larger stimulation amplitudes (>2 T) are needed to inhibit bladder function. Not only are these amplitudes markedly higher than those used clinically in humans, but these findings also suggest that bladder inhibition is achieved, at least in part, by electrical recruitment of smaller diameter (Aδ) myelinated fibers as well as co-activation. Preliminary work in the inventors laboratory (PY) at the University of Toronto using a rat model has also shown that stimulation of the SAFN which innervates the entire medial side of the lower leg—can evoke bladder-inhibitory reflexes, and further that it can do so using amplitudes that are as low as 25% of those used for PTN.

The anatomical proximity of the PTNS electrode (an uninsulated needle) to SAFN branch(es) that innervate and also pass through the region posterior to the medial malleolus also motivated this study. Studies in human cadavers show that a major posterior SAFN branch is found in approximately 87% of sampled subjects. This led us hypothesize that benefits of PTNS therapy may often involve concomitant activation of a portion of SAFN fibers. Given the challenges of testing this hypothesis in patients, we conducted a computational study that simulated PTNS in a model of the human lower leg. The effects on the relative electrical recruitment of the TN and SAFN for needle electrode location, needle electrode type (uninsulated vs. insulated) and stimulation amplitude were explored.

FIG. 16, shows a cross section of the human ankle used to model the PTN and SAFN (a hypothetical distribution of 5 branches labeled S-A to S-E) that was extruded to a depth of 20 cm. (left side) and also shows that the relative activation of the TN and SAFN branches achieved by PTNS was strongly dependent on the depth and anterior-posterior position of the uninsulated (top row) and insulated (bottom row) needle. The model predicts that—when compared to the PTN—the uninsulated needle will activate SAFN (branches A-to-C and branches D-E) at lower amplitudes when the electrode is located more posterior or superficial to the PTN, respectively. In contrast (bottom row), the insulated needle is markedly more selective in electrically activating the PTN (i.e., lower threshold than SAFN) across the 5×10 grid. The top row clearly shows that with an un-insulated needle, the spread of co-activation is prevalent. Two different methods were used to predict excitation of the PTN and SAFN: the activating function (AF) and the McIntyre-Richardson-Grill (MRG) axon model. Within a 5×10 array of needle electrode positions (spacing between grid locations=0.2 cm), electrical stimulation was simulated at each location using various stimulation amplitudes relative to PTN threshold (0.5 T to 4 T). At each location the relative excitability of PTN and SAFN was quantified by a selectivity ratio (SR) (ratio of the AF of the PTN to the AF of the SAFN), reflecting the relative activation of the two target types. At each level of PTN stimulation (0.5 T to 4 T), the % of electrically-activated SAFN branches was also determined using the MRG model.

FIG. 17 plots the percentage change in SR and indicates the average decrease in threshold for activating a SAFN branch can be between about 100% (branches A, B, and E) and 10,000% (branches C and D), when the insulated electrode is replaced with an uninsulated electrode.

FIG. 18, plots the percentage of SAFN branches that are activated when electrical stimulation is applied at each location within the 5×10 grid (top row: uninsulated needle, bottom row: insulated needle). When applying PTNS with an uninsulated needle (as occurs clinically in patients), the computational model shows that significant co-activation of SAFN is achieved, not only at amplitudes equal to or greater than the foot motor threshold (≥1 T) but also at amplitudes below IT. Depending on the location of the electrode tip, anywhere between 20% and 100% of SAFN branches are activated by the PTNS electrode. In contrast, electrical stimulation delivered with an insulated needle appears more effective at avoiding SAFN branch activation. However, as shown in FIG. 19, selective PTN activation is possible only when the electrode tip is placed within approximately 0.2 cm (1 T) to 0.02 cm (4 T) from the TN.

FIGS. 16 to 19 results suggest that in humans it is extremely likely that percutaneous stimulation of the PTN with an uninsulated needle provides unintended activation of SAFN fibers. Co-activation of SAFN fibers during PTNS can potentially influence the therapeutic outcome in patients by providing at least supplementary, if not primary, bladder inhibitory effects. Further, results from this computational study suggested that targeting the SAFN directly may provide improved therapeutic response. We have now shown in humans using percutaneous stimulation of the SAFN near the knee which is unlikely to co-activate any tibial nerve fibers.

These data may support an embodiment of a method for modulating voiding activity of a patient that comprises the steps of implanting at least one electrode and applying a stimulation signal from the implanted electrode while the electrode is closer to the SAFN than the PTN to provide improved benefit. If the electrode is multipolar and is configured to use field steering then the method may include using multiple contacts to steer the field towards a SAFN target. Alternatively, both the SAFN and PTN can be stimulated more reliably by spatially directed fields and/or well positioned electrodes specifically oriented towards each target. Accordingly, if a coin-shaped neurostimulator is implanted near the PTN, electrode contacts can be provided on its top and bottom surfaces to achieve selective neurostimulation.

A preclinical study was conducted in twenty-three Sprague-Dawley rats, where animals were initially anesthetized under isoflurane (3-5%) and later transitioned to urethane following surgical procedures (1.2 g/kg, IP). The bladder dome was catheterized and connected in series to a pressure transducer and infusion pump. An incision along the medial aspect of the lower leg provided access to the SAFN, caudal to the knee joint where a bipolar stimulating nerve cuff electrode was placed. A pair of de-insulated stainless steel wire electrodes was inserted into the external urethral sphincter (EUS) muscle using a perineal approach. The bladder was emptied and then continuously filled with saline (infusion rate=0.08−0.1 ml/min) throughout the experiment. Reflex bladder contractions were confirmed by rapid increases in pressure with concomitant bursting EUS activity.

Bladder function was quantified by the bladder contraction rate (BCR). A total of 121 stimulation trials were conducted where the pulse width was set at 200 us while the stimulation parameters were varied as follows: Frequency: 2 Hz-50 Hz; Amplitude: 25 uA-100 uA; Duration: 10 min-40 min. The baseline BCR averaged to 0.6±0.12 contractions/min.

As shown in FIG. 20, low amplitude stimulation trials (10-minutes each) at 20 Hz was most effective at achieving significant reductions in the average BCR (50.2±5.0%, range: 33.8%-78.1%), during both the intra-stimulation and post-stimulation (38.7±6.2%) periods. As shown in FIG. 21, the effectiveness of SAFN stimulation was also confirmed by the very high percentage of rats that exhibited an inhibitory response at 20 Hz (100%).

The decrease in bladder activity seen in rat data should reduce both frequency of voids and urgency related to voids in humans. In order to determine if therapy is providing benefit the system can be configured to ask users about their symptoms. Accordingly, FIG. 22 shows a screen asking a user to provide input about bathroom frequency while FIG. 23 shows a screen asking a user to provide input about urgency. The responses to these questions can be stored and can guide therapy as will be disclosed.

FIG. 24 shows that by increasing the duration of the stimulation trial (amplitude set at 25 μA), we observed a growth in instances where bladder function was markedly inhibited (i.e., atonic bladder). This loss in bladder function occurred in 20% of experiments following 20 minutes of 10 Hz SAFN stimulation, and in 50% of experiments following 40 minutes of 10 Hz SAFN stimulation. It was less frequently observed following 20 Hz SAFN stimulation. This stimulation-evoked loss in bladder function is shown in FIG. 25, where long duration (40 minute) continuous stimulation of SAFN at 10 Hz is coupled to low stimulation amplitudes. After an initial decrease in BCR (i.e., longer intervals between contractions) during the intra-stimulation period, we observe a gradual transition towards a loss in bladder function near the end of the stimulation trial period. This was characterized by a gradual increase in the basal (i.e., resting) bladder pressure, a significant decrease in the bladder contraction amplitude (49.0±10.5%), and also an increase in the threshold bladder pressure at which voiding occurs (17.6±4.8%). This transition period is followed by random fluctuations in bladder pressure along with passive leaks (single drops) through the urethral meatus. The duration of this loss in bladder function was approximately 30 to 50 minutes.

When considering these pre-clinical data, effective clinical treatment of OAB symptoms with at least SAFN stimulation may be achieved at (1) the highest amplitude tolerated by patients, (2) frequency set at 10 Hz or 20 Hz, and (3) electrical stimulation applied for longer periods (e.g., 5 or 10 hours per day) in more severe patients. Alternatively, it may be found in patients that electrical stimulation at the sensory threshold, with as little as 30 minutes every week is sufficient to produce improvements in OAB symptoms. The post-stimulation response evoked by SAFN stimulation in this preclinical data may be akin to what is seen in humans following PTNS. While additional work is needed to characterize the reflex pathways for SAFN stimulation, this preclinical work provides evidence that supports the potential for using SAFN stimulation to treat patients.

eTENS

In embodiments of the invention the neurostimulator uses an external stimulator such as a TENS surface electrode and an implanted passive component (IPC) which can be realized as a conductive nerve cuff, conductive rod, a thin conductive plate or mesh that is suitably configured with an anchoring means in order to maintain its position in a patient, or even a conductive gel. FIG. 26 and FIG. 27 show a modeled embodiment of a surface electrode, target nerve surrounded by tissue and local anatomy, and an IPC. Systems and methods related to the inventive principles that are now described are termed enhanced transcutaneous electrical stimulation or “eTENS”. The eTENS principles are still being evaluated and the data provided here are shown for illustrations purposes and are not intended to be limiting.

FIG. 28 shows a schematic of a circular TENS electrode 30N which is configured to provide monopolar stimulation. A second TENS (return) electrode is located far away on the skin of the patient (not shown in diagram). An IPC 212 that is separated from the TENS electrode at its proximal end by a distance 211A and its distal end by a distance 211B, which are approximately equal. The IPC is also separated from the target nerve at its proximal end (212A) by a distance 211C and its distal end (212B) by a distance 211D. The figure is not to scale and the distance 211C an 211D are typically made to be as small as possible so that the IPC is either in contact with the target nerve, or almost in contact. In this example the IPC is implanted to be aligned with the target nerve. If the target nerve is not parallel to the skin surface and TENS electrode then 211A may be larger or smaller than 211B, but the distance 211C and 211D should remain approximately equal so that the IPC is aligned with the nerve approximately along its total length or for the majority of its length. Accordingly, the IPC is not designed to serve as a conduit which physically routes electrical charge from a pulse generator (or a relay device such as a receiver terminal) to a target nerve. Instead, evidence is shown here supporting that the enhancement of neural activation is achieved by a different mechanism that modifies the electrical current passing through and around the IPC, as well as the target nerve.

Although the figure shows a monopolar montage, in order to realize the eTENS system, the interface ports 83 of the neurostimulator 50 can communicate with bipolar electrode components including two contacts separated by space or a non-conductive surface that has been paired with the IPC length and positioned relative to the IPC to provide improved eTENS. The two contacts may serve as an anode and cathode respectively or may both be anode or cathode with another electrode, located elsewhere, serving to complete the circuit. The anode and cathode status can change as a function of the stimulation waveform.

FIGS. 29a-c show the effects of eTENS (measured by relative excitation) are dependent on the relative location of the IPC (e.g., nerve cuff) and the surface electrode. In this example, the IPC achieves more ‘enhancement’ when the nerve cuff is located at the edge of the TENS electrode that corresponds to where the return electrode is located. The return electrode is located at a position greater than 16 cm along the nerve (refer to x-axis). The TENS electrode is represented as the dark bar near the x-axis, while each data point corresponds to the mid-point of the IPC. The black bar in each plot reflects the length of the TENS electrode, and the IPC is 1 cm. Monopolar stimulation is modeled.

FIG. 30 shows that ‘enhancement’ of neural activation is achieved when the electrical conductivity of the IPC is at least 3 orders of magnitude greater than that of saline (˜1 S/m). FIG. 31 shows that the effects of eTENS can be further increased by increasing the length of the IPC.

As part of the mechanism of eTENS, which is different from routing the stimulus current, FIG. 32 shows that the electric potential along the nerve cuff and within the endoneurim. The nerve cuff creates an isopotential surface within the body; while the endonerium shows an electric potential gradient that varies spatially along the nerve. The inset is shown, in an expanded view, at the top of the figure.

FIGS. 33A to 33D show radial and axial current characteristics along a peripheral nerve with a length of 20 cm. The TENS electrode is centered at the 10 cm location, and the IPC is centered at 16.5 cm. The goal of placing the IPC distal to the TENS electrode was to show the effect of the IPC on the externally applied stimulus current. Compared to conventional TENS, FIGS. 33A and 33C show that the IPC generates radial currents at the site of implant. In FIGS. 33B and 33D, the axial (i.e., longitudinal) current along the nerve decreases by over 50% within the IPC. The amplitudes used in these simulations are sub-threshold to nerve activation. The positive radial current at the outer surface of the endoneurim (centered at 10 cm) is indicative of the cathodic current applied through the surface electrode. The radial current generated at the nerve cuff, which is located 7.5 cm distal to the center of the surface electrode, appears as a virtual anode-cathode pair. In FIG. 33B the longitudinal current is largest between the surface electrode and the distal ground, but the presence of the nerve cuff causes a very large decrease in the longitudinal current within this highly-conductive cylindrical shell.

FIG. 34A provides visualization of current density vectors generated by a simulation of eTENS (corresponding data shown in FIG. 33A-D). An influx of current is seen within the proximal half of the IPC (closer to the active TENS electrode) and an efflux of current is observed within the distal half of the IPC (closer to the return electrode). The current density vectors point in the opposite direction when looking outside the IPC. Current is pointed away from the proximal half of the IPC; whereas the current is drawn towards the distal half of the IPC. This is created in part by the isopotential surface of the nerve cuff. On the right side of the figure the potential in the nerve cuff is lower than the potential in the surrounding tissue and so current flows towards the nerve cuff, while on the left side of the figure current flows into the surrounding tissue. This phenomenon is explained by (1) the electric potential gradient created between the (anodic) return electrode (electrical ground) and the cathodic TENS electrode (negative potential) and (2) the isopotential field of the IPC. The proximal half of the IPC is at a higher potential than its surroundings (both inside and outside the cuff); while the opposite is true for the distal half of the IPC. As a result, current will flow away from the proximal half of the IPC; and current will flow towards the distal half of the IPC. In effect, the IPC serves as a ‘virtual’ cathode. The corresponding ‘activating function’ of a single nerve fiber shows positive values (i.e., depolarization) within the distal half of IPC, which suggests a ‘virtual cathode’ is created by the eTENS system (see FIG. 34B). FIGS. 27-34 are based upon a study that will be reported in Enhanced peripheral nerve stimulation technique for treating overactive bladder: A computational model of tibial nerve stimulation in humans, Roointan, Elder, and Yoo, (In Prep.), incorporated by reference herein.

In accordance with the data provided herein the following embodiments are supported which do not require rectification of wireless energy using a coil or rectenna or any circuitry which incorporates this novel phenomenon into the inventive design.

In an embodiment, a transcutaneous nerve tissue stimulation system includes a stimulation module having at least one electrical stimulus generator and at least a first stimulator, such as a TENS electrode, that is electrically connected to the electrical generator. The stimulator is adapted to be positioned on the surface of the skin of a patient to provide at least one electrical stimulation signal to the patient. The system further includes at least a first implanted member that is an electrically conductive surface or volume, such as a conductive nerve cuff, conductive rod, or strip of conductive material. The implanted member being positionally located adjacent to or contiguous with a target nerve tissue.

In an embodiment, the implanted member is located at a predetermined depth below the skin surface of a patient for enhancing the activation of said target nerve tissue by a signal provided by the stimulator, and the signal provided by the stimulator is a function of at least the size of the stimulator and the predetermined depth of said target tissue.

In an embodiment, the first implanted member has a portion thereof being electrically conductive and is devoid of circuitry such as coils, antennae, integrated circuits, diodes, and the like with respect to converting power provided by the TENS electrode.

In an embodiment, the electrical stimulus generator drives a magnetic transducer having a one or more coils for inducing a field near a target nerve and in the area of the implanted conductive member, and the implanted member serves to enhance the activation of the target tissue, relative to what would occur in the absence of the implanted member.

In an embodiment, the at least first stimulator 30N and the at least first implanted member 212 are displaced each from the other by tissue which is devoid of an intervening implanted conductive member extending therebetween. Further, the implanted member 212 is also devoid of any non-conductive insulating material that is designed to allow electrical current to be routed from a pick-up electrode relatively close to the surface of the skin to a stimulating electrode located relatively distal to the skin and relatively proximal to a tissue target, for routing a stimulation signal therebetween.

In an embodiment, the implanted member 212 is positionally located with the majority of its length disposed adjacent to, and approximately parallel with, a portion of the target nerve tissue such that it is located at approximately a depth below the skin surface of a patient and enhances the activation of the target nerve by a signal provided by the stimulator. The stimulation signal is conducted solely through intervening tissue (e.g., dermis) of the patient.

In an embodiment, the distal 212 a and proximal 212 b tips of the implantable conductive member, that is devoid of circuitry for converting the field of the stimulus signal into a stimulation signal, are both located approximately adjacent to the target nerve. The proximal end 212 b will not be substantially closer to the surface stimulator than the distal tip 212 b, or vice versa, unless the target nerves travels from a deep site, to a relatively superficial site in the patient. Both the distal and proximal sides of the implanted component will typically be approximately the same distance from the surface of the skin of the patient. The implanted member is positionally located adjacent to or contiguous with a target nerve tissue such that it is adjacent to the nerve for approximately the span of its entire length for enhancing the activation of target nerve tissue by a signal provided by the stimulator. The enhancement will be a function of, for example, the distance between the target nerve and the surface of the patient's skin, the size of the implanted component (e.g., length), and the size of the surface electrode.

In embodiments related to eTENS (or TENS), high frequency current bursts (e.g., greater than 10 kHz or 1 MHz) can be provided using TENS electrodes at the surface of the skin across the tissue where the one or more implants are located. Although the implantable components often act to stimulate target tissue with stimulation signals that approximate those delivered by a stimulator at the skin surface, depending upon factors such as the distance from the surface and the conductivity of the implants these may act as low pass filters of these high frequency current bursts, and can generate focused low frequency currents capable of stimulating excitable nerve, muscle, or other tissue. When one or more implantable components are used to modulate biological activity such as altering the function of an internal organ (e.g. vagus nerve for modulating an inflammatory response, cardiac activity, or appetite of an organism) these may be used as so-called “electroceuticals”.

In an embodiment, a system component such as the physician programmer 70 provides simulation modeling using a simulation module 57 related to therapy and model result data. These result data may be used by a physician, or can be operated upon by control circuitry of a neurostimulation system, to adjust and control the stimulation circuitry in order to provide stimulation to the patient according to a stimulation protocol which is adjusted to provide eTENS. In an embodiment, the computer module performing the simulation is adjusted based upon imaging data scanned from a patient, such as collected MRI or sonography in order to reflect the physical characteristics of an area of a patient's body within which the stimulation target is located. Stimulation may include the activation and control of a stimulation grid array (in which elements of the array can be activated to create different electrode spacing) or a set of spatially discrete stimulators that are configured or operated according to results provided by the simulation with the goal of increasing the probability that stimulation will successfully modulate target tissue by improving eTENS. In an embodiment, a grid electrode can allow the electrically active area of a monopolar electrode to functionally be longer or shorter by activating more or less electrode contacts on the ventral surface of the grid electrode. This may provide an advantage since FIGS. 29A-C show that increasing the length of the TENS electrode can increase the relative excitation of the target nerve. The adjustment of length can also be used to increase patient comfort (e.g. longer length of active monopole), unless this results in unwanted muscle activation or other side effects. Additionally, rather than using entire rows during an activation, the array stimulator can activate the electrode contact elements 1-4 of row 1, elements 5-8 of row 4, and elements 9-12 of row 8. Rather than horizontal rows, the grid stimulator can also activate other patterns such as a diagonal row in order to provide stimulation arrays that are oriented correctly with respect to the edges of the IPC. The grid array can provide arbitrary activation patterns rather and grid element shapes.

The modules described for the apparatus 50 are for illustration purposes only and the subject invention can have less than or more than the modules and system components described in this specification, or can be realized in alternative embodiments. For example, rather than having a protocols and parameters module 66, the information related to stimulation protocols and parameters can be simply stored in the memory module 60. Disclosed components and modules may be omitted and modules may communicate with, and share, resources of other modules. Any of the system components or modules can be realized partially or fully in the physician/patient programmer 70, remote computer 70′, or neurostimulation system 50. The modules may reside within the device 50 housing or may exist externally and communicate. The apparatus 50 may be realized as a portable or desktop instrument that controls accessories. The system can be implemented, at least in part, as customized hardware that operates with a smart-phone or tablet computer or which communicates with the smartphone or computer so that some disclosed modules are realized by the smart phone or computer.

The subject systems and methods may be realized using various instruments and stimulators distributed by companies such as Uroplasty, Electrocore, Medtronic, StimGuard, Halo Neuroscience (e.g., tDCS, tACS), and eNEURA (e.g., TMS), for providing various types of stimulation. This includes electrical, magnetic, microwave or other stimulation directed either to implantable components that stimulate tissue or to the tissue itself. Stimulation provided by at least one of TENS, eTENS, percutaneous, external, partially or fully implantable systems can be operated to provide stimulation using the protocols and nerve targets disclosed herein. Patients (including children with urinary disorders) may be treated with either TENS, percutaneous, or implanted devices as a means of reducing their OAB symptoms that include incontinence and nocturia, or treating various pelvic floor disorders by SAFN stimulation.

The term OAB is used herein can be generally be understood to include disorders such as incontinence, bladder pain, fecal incontinence, and pelvic floor disorders and their symptoms. Treatment can include relief from symptoms, improvement of abnormal activity, etc.

The foregoing description of preferred embodiments for this disclosure have been presented for purposes of illustration and description. They are not intended to limit the invention to the precise forms disclosed. Obvious modifications or variations are possible in light of the above teachings. The different embodiments are chosen and described in an effort to provide the best illustrations of the principles of the invention and its practical application, and to thereby enable one of ordinary skill in the art to utilize the invention in various embodiments and with various modifications as are suited to the particular use contemplated. All these modifications and variations are within the scope of the invention as determined by the appended claims when interpreted in accordance with the breadth to which they are entitled. 

We claim:
 1. A method of assessing stimulation and treating an overactive bladder of a patient comprising: establishing at least one stimulator adapted to treat an overactive bladder of the patient; establishing a neurostimulator configurable to provide a treatment stimulation signal to said at least one stimulator according to a stimulation protocol that is adapted to stimulate a saphenous nerve of the patient for the treatment of the patient's overactive bladder; positioning the at least one stimulator on the inner side of the patient's leg and adjacent the saphenous nerve in the area near an upper calf region of the patient's leg; actuating said neurostimulator to provide a test stimulation signal and assessment; and determining by response from the patient if at least one sensation is experienced which radiates away from the location of the at least one stimulator; whereby (1) when application of the test stimulation signal fails to produce a radiating sensation indicating that the saphenous nerve has been stimulated, then performing the step of either increasing the test stimulation signal or adjusting the position of the at least one stimulator, and (2) when the test stimulation signal produces the radiating sensation, then providing stimulation treatment using a stimulation signal strength which is set to a value strength that produces the radiating sensation and is below a value strength that is painful to the patient.
 2. The method of claim 1, wherein the step of determining if a sensation occurs includes the step of determining if the sensation is radiating away from at least one stimulator and down the leg towards or into the foot.
 3. The method of claim 1, further including the steps of providing instructions to place a second lower electrode so that it is vertically displaced from a first electrode and near the medial malleolus or the sole of the foot and determining if a sensation occurs which is at least one of: radiating away from the first electrode and down the leg, or away from the second lower electrode and up the leg.
 4. The method of claim 1, including providing user instructions related to actuating said neurostimulator to provide a test stimulation signal and perform assessment wherein said user instructions include at least one of: a. written instructions; b. illustrations of the leg with graphic depictions of the location on the medial surface of the leg where the TENS electrodes should be placed; c. illustrations of the leg with graphic depictions of the location on the medial surface of the leg where a TENS array should be placed; d. instructions provided by a mobile device app or a mobile device; e. an audio-message of instructions; f. verbal instructions; g. instructions to use a device such as an ultrasound, infrared, or electrical impedance device in order to locate the saphenous nerve or saphenous vein; h. instructions provided in combination with either a virtual reality or holographic display; i. instructions provided by a mixed media technology such as a DVD, and, j. a website address where user instructions are provided.
 5. The method of claim 1, wherein said at least one stimulator is at least two transcutaneous electrical nerve stimulators (TENS) electrodes realized as part of an accessory such as an electrode array that positions the electrodes on the medial aspect of a patient's leg.
 6. The method of claim 1, wherein said at least one stimulator is at least two transcutaneous electrical nerve stimulators (TENS) electrodes realized within an electrode array that is connected to at least one band that is configured to be wrapped around the calf of a patient and to position the array vertically along the inner side of the leg and having at least a first electrode positioned above at least a second electrode.
 7. The method of claim 1, further including at least one wearable band that is configured to be attached to at least one electrode and to wrap around the area of a patient's (1) upper calf, (2) mid-calf, or (3) entire leg to secure and bias the at least one electrode to an area between the upper calf muscle and the tibia.
 8. The method of claim 1, further including operating an external patient programmer which is configured to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and external patient programmer are configured to monitor usage and assess compliance with respect to a treatment program that is related to treatment of overactive bladder.
 9. The method of claim 1, further including establishing an external patient programmer which is configured to obtain user input and to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and external patient programmer is configured to provide patient alert reminders related to a stimulation program that is defined for the treatment of overactive bladder.
 10. The method of claim 1, further including providing an external patient programmer which is configured to obtain user input and to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and external patient programmer are configured to query about bladder activity, bladder pressure, urinary leakage and/or urgency episodes measured by at least one wearable sensor or at least one implantable sensor.
 11. The method of claim 1, further including establishing an external patient programmer which is configured to obtain user input and to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and the external patient programmer are configured to query the patient about a symptom characteristic such as severity or frequency related to overactive bladder symptoms and to store the response.
 12. The method of claim 1, further including establishing an external patient programmer which is configured to obtain user input and to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and external patient programmer are configured to allow the patient to input information related to a bladder diary, including if a void event was associated with urgency or leakage.
 13. The method of claim 1, further including providing an external patient programmer which is configured to obtain user input and to communicate with and provide user control of the neurostimulator wherein at least one of the neurostimulator and external patient programmer are configured to query the patient to input information about at least one of: whether any voiding events occurred during night, whether voiding events awoke the patient, whether voiding events were accompanied by urgency or leakage.
 14. The method of claim 1, further including providing instructions related to setting a stimulation protocol that is defined for stimulation of the saphenous nerve for the treatment of the patient's overactive bladder which includes setting the stimulation signal to be at least one of: a signal between 5 and 20 Hz, a 10 Hz signal, a 20 Hz signal, and a signal that roves between 10 and 20 Hz.
 15. The method of claim 1, wherein the stimulation signal strength is defined as a function of at least one of: skin threshold (Tskin), maximum tolerance (Tmax), and a signal that roves between Tskin and Tmax, by continuously or periodically adjusting amplitude, stimulus pulse width, and/or period in the case of a sinusoidal waveform.
 16. The method of claim 1, further including establishing an external patient programmer wherein the external patient programmer is configured to graphically display data related to overactive-bladder-related symptoms as summary statistics or trend charts.
 17. The method of claim 1, further including establishing an external device or programmer wherein the external device or programmer determines the therapeutic protocol for a given week or longer periods based upon at least one of: time since the start of therapy, number of stimulation sessions provided since the start of therapy, rate of stimulation sessions provided since the start of therapy, and improvements, worsening, or no change in symptoms as calculated upon patient input data.
 18. The method of claim 1, wherein the neurostimulator is further provided with an accelerometer and is configured to analyze the accelerometer data including activity data and orientation data, in order to determine using at least one of activity data and orientation data if a user is likely doing at least one activity of: walking, getting out of bed, or moving with a gait that is over a selected rate, and if so then making a modification of the operation of the stimulus generator which may include pausing or decreasing the provision of stimulation until analysis of the accelerometer data determines that the user has stopped the activity.
 19. The method of claim 1, wherein the at least one stimulator is selected from the group of: at least two transcutaneous electrical neural stimulation (TENS) electrodes, and at least one magnetic stimulator.
 20. The method of claim 1, wherein the radiation sensation includes at least one of the group of: a tingling, vibrating, buzzing, pressure, electrotactile tactile sensation, warmth, and tickling. 